Systems, catheters, and methods for treating along the central nervous system

ABSTRACT

Systems, catheters, and methods for accessing and treating along the central nervous system are disclosed. An example method may manage inflammation of the patient to treat a condition of the patient by processing values related to one or more physiological parameters of a patent, identifying when an inflammation condition of the patient has reached a treatment condition based on the processed values, and automatically providing an indication that the inflammation condition has reached the treatment condition. An example indication may include actuation of a treatment protocol. The example method may be performed with an inflammation management system.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority under 35 U.S.C. § 119 toU.S. Provisional Application Ser. No. 62/716,335, filed Aug. 8, 2018;and U.S. Provisional Application Ser. No. 62/844,566, filed May 7, 2019,the entirety of which are incorporated herein by reference.

TECHNICAL FIELD

The present disclosure relates to systems, modules, and methods fordiagnosing and treating along the central nervous system.

BACKGROUND

A wide variety of medical devices, systems, and methods have beendeveloped for medical use. Some of these devices, systems, and methodsinclude control systems, pumps, guidewires, catheters, and the like.These devices and systems are manufactured by any one of a variety ofdifferent manufacturing methods and may be used according to any one ofa variety of methods. Of the known medical devices, systems, andmethods, each has certain advantages and disadvantages. There is anongoing need to provide alternative medical devices as well asalternative methods for manufacturing and using medical devices.

SUMMARY

This disclosure provides design, material, manufacturing method, and usealternatives for medical devices and/or systems. One example includes aninflammation management system. The system comprises: a controller; acerebrospinal fluid management module in communication with thecontroller; wherein the controller is configured to: monitormeasurements of one or more physiological parameters of a patient;compare a value related to the monitored measurements of the one or morephysiological parameters to a threshold value; and control thecerebrospinal fluid management module based on the comparison of thevalue related to the monitored measurements of the one or morephysiological parameters to the threshold value.

Alternatively or additionally to any of the embodiments above, whereinthe controller is configured to automatically control the cerebrospinalfluid management module to perform a treatment on cerebrospinal fluid ofthe patient when the value related to the monitored measurements of theone or more physiological parameters reaches or goes beyond thethreshold value.

Alternatively or additionally to any of the embodiments above, whereinthe treatment on cerebrospinal fluid of the patient is a predeterminedtreatment based on a type of physiological parameter associated with themonitored measurements.

Alternatively or additionally to any of the embodiments above, whereinthe treatment on cerebrospinal fluid of the patient is a predeterminedtreatment based on the comparison of the value related to the monitoredmeasurements of the one or more physiological parameters and a type ofphysiological parameter associated with the monitored measurements.

Alternatively or additionally to any of the embodiments above, whereinthe value related to the monitored measurements of the one or morephysiological parameters is an indexed value related to measurements oftwo or more physiological parameters of the patient.

Alternatively or additionally to any of the embodiments above, whereinthe indexed value is a value of an index based on measurements of thetwo or more physiological parameters of the patient.

Alternatively or additionally to any of the embodiments above, whereinthe indexed value is a value of an index based on two or more ofsub-indices and each sub-index of the two or more of sub-indices isbased on measurements of two or more physiological parameters of thepatient.

Alternatively or additionally to any of the embodiments above, whereinthe value related to the monitored measurements of the one or morephysiological parameters is a value of a measurement of a physiologicalparameter of the one or more physiological parameters.

Alternatively or additionally to any of the embodiments above, whereinthe one or more physiological parameters include one or morephysiological parameters selected from a group consisting ofintracranial pressure, cerebral pressure perfusion, mean arterialpressure, heart rate, brain oxygenation, cerebral blood flow, and acytokine level.

Alternatively or additionally to any of the embodiments above, whereinthe cerebrospinal fluid management module comprises a cooling treatmentmodule.

Alternatively or additionally to any of the embodiments above, whereinthe cerebrospinal fluid management module comprises a filtrationtreatment module.

Alternatively or additionally to any of the embodiments above, whereinthe cerebrospinal fluid management module comprises a cooling treatmentmodule and a filtration treatment module.

Alternatively or additionally to any of the embodiments above, whereinthe cerebrospinal fluid management module comprises a circulation modulehaving a pump configured to pump cerebrospinal fluid from the patient toa treatment module.

Alternatively or additionally to any of the embodiments above, furthercomprising: a communications port in communication with the controller;and wherein the communications port is configured to receive themeasurements of the one or more physiological parameters of a patientthat are monitored by the controller.

Alternatively or additionally to any of the embodiments above, furthercomprising: a communications port in communication with the controller;and wherein the communications port is configured to facilitatecommunication between the cerebrospinal fluid management module and thecontroller.

Alternatively or additionally to any of the embodiments above, furthercomprising: a wireless communications port in communication with thecontroller and configured to facilitate communication between thecontroller and a device over a wireless network.

Alternatively or additionally to any of the embodiments above, furthercomprising: a user interface in communication with the controller; andwherein the user interface is configured to receive inputs that modifyan operation of the controller.

Alternatively or additionally to any of the embodiments above, whereinthe user interface is configured to display a medical image of thepatient in a selectable pane and one or both of the measurements of theone or more physiological parameters of a patient and the value relatedto the monitored measurements of the one or more physiologicalparameters in a real-time updating pane position on the user interfaceadjacent the selectable pane.

Another example includes a cerebrospinal fluid circulation system. Thesystem comprising: a controller; a circulation management module incommunication with the controller; a cerebrospinal fluid treatmentmanagement module in communication with the controller; wherein thecontroller is configured to automatically control the circulationmanagement module and the cerebrospinal fluid treatment managementmodule based on measurements of one or more physiological parameters ofa patient.

Alternatively or additionally to any of the embodiments above, whereinthe controller is configured to control the circulation managementmodule to maintain a predetermined cerebrospinal fluid flow rate.

Alternatively or additionally to any of the embodiments above, whereinthe controller is configured to control the circulation managementmodule to maintain a cerebrospinal fluid pressure at or below a setpoint level.

Alternatively or additionally to any of the embodiments above, whereinthe cerebrospinal fluid management treatment module is configured toinclude one or more exchangeable treatment modules.

Alternatively or additionally to any of the embodiments above, whereinthe one or more exchangeable treatment modules include one or moretreatment modules selected from a group consisting of a coolingtreatment module and a filtration treatment module.

Alternatively or additionally to any of the embodiments above, whereinthe cerebrospinal fluid treatment management module includes a coolingtreatment module.

Alternatively or additionally to any of the embodiments above, whereinthe controller is configured such that when the controller determines avalue related to a measurement of a physiological parameter of a patientreaches or goes beyond a threshold value, the controller adjustsoperation the circulation management module to actively draincerebrospinal fluid while adjusting operation of the cooling treatmentmodule to cool cerebrospinal fluid for a predetermined time period.

Alternatively or additionally to any of the embodiments above, whereinthe cerebrospinal fluid treatment management module includes afiltration treatment module.

Alternatively or additionally to any of the embodiments above, whereinthe controller is configured such that when the controller determines avalue related to a measurement of a physiological parameter of a patientreaches or goes beyond a threshold value, the controller adjustsoperation of the circulation management module to circulatecerebrospinal fluid at a predetermined rate while adjusting operation ofthe filtration treatment module to filter a contaminant fromcerebrospinal fluid.

Another example includes a method of managing inflammation. The methodcomprising: monitoring measurements of one or more physiologicalparameters of a patient over time; comparing a value related to themonitored measurements of the one or more physiological parameters to athreshold value; and adjusting operation of a cerebrospinal fluidmanagement module based on the comparison of the value related to themonitored measurements of the one or more physiological parameters tothe threshold value.

Alternatively or additionally to any of the embodiments above-furthercomprising: determining a difference between the value related to themonitored measurements of the one or more physiological parameters andthe threshold value; and wherein the adjusting operation of thecerebrospinal fluid management module is based on the determineddifference between the value related to the monitored measurements ofthe one or more physiological parameters and the threshold value.

Alternatively or additionally to any of the embodiments above, whereinthe adjusting operation of the cerebrospinal fluid management module isautomatically initiated based on the comparison of the value related tothe monitored measurements of the one or more physiological parametersto the threshold value.

Alternatively or additionally to any of the embodiments above, whereinthe adjusting operation of a cerebrospinal fluid management moduleinitiates a treatment start protocol in response to the value related tothe monitored measurements of the one or more physiological parametersreaching or going beyond the threshold value a first time.

Alternatively or additionally to any of the embodiments above, whereinthe adjusting operation of a cerebrospinal fluid management moduleinitiates a treatment stop protocol in response to the value related tothe monitored measurements of the one or more physiological parametersreaching or going beyond the threshold value a second time afterreaching or going beyond the threshold value the first time.

Alternatively or additionally to any of the embodiments above, whereinthe adjusting operation of a cerebrospinal fluid management moduleinitiates a treatment stop protocol in response to the value related tothe monitored measurements of the one or more physiological parametersreaching or going beyond the threshold value.

Alternatively or additionally to any of the embodiments above, whereinthe adjusting operation of a cerebrospinal fluid management moduleinitiates a predetermined treatment protocol based on a type ofphysiological parameter associated with the monitored measurements.

Alternatively or additionally to any of the embodiments above, whereinthe adjusting operation of a cerebrospinal fluid management moduleinitiates a predetermined treatment protocol based on the comparison ofthe value related to the monitored measurements of the one or morephysiological parameters to the threshold value and a type ofphysiological parameter associated with the monitored measurements.

Alternatively or additionally to any of the embodiments above, whereinthe adjusting operation of a cerebrospinal fluid management modulecauses the cerebrospinal fluid management module to initiate a coolingtreatment protocol.

Alternatively or additionally to any of the embodiments above, whereinthe adjusting operation of a cerebrospinal fluid management modulecauses the cerebrospinal fluid management module to initiate afiltration treatment protocol.

Alternatively or additionally to any of the embodiments above, whereinthe adjusting operation of a cerebrospinal fluid management modulecauses the cerebrospinal fluid management module to initiate afiltration treatment protocol and a cooling treatment protocol.

Another example includes a computer readable medium having storedthereon in a non-transitory state a program code for use by a computingdevice, the program code causing the computing device to execute amethod for managing inflammation, the method comprising: determining avalue related to one or more measurements of one or more physiologicalparameters; comparing the value related to the one or more measurementsof the one or more physiological parameters to a threshold value; andoutputting a control signal to adjust operation of a cerebrospinal fluidmanagement module based on the comparison of the value related to theone or more measurements of the one or more physiological parameters tothe threshold value.

Alternatively or additionally to any of the embodiments above, themethod further comprising: determining a difference between the valuerelated to the one or more measurements of the one or more physiologicalparameters and the threshold value; wherein the control signal adjustingoperation of the cerebrospinal fluid management module is based on thedetermined difference between the value related to the one or moremeasurements of the one or more physiological parameters and thethreshold value.

Alternatively or additionally to any of the embodiments above, whereinthe outputting of the control signal is automatically initiated based onthe comparison of the value related to the one or more measurements ofthe one or more physiological parameters to the threshold value.

Alternatively or additionally to any of the embodiments above, whereinthe outputted control signal adjusting operation of a cerebrospinalfluid management module is configured to initiate a treatment startprotocol in response to the value related to the one or moremeasurements of the one or more physiological parameters reaching orgoing beyond the threshold value a first time.

Alternatively or additionally to any of the embodiments above, whereinthe outputted control signal adjusting operation of a cerebrospinalfluid management module is configured to initiate a treatment stopprotocol in response to the value related to the one or moremeasurements of the one or more physiological parameters reaching orgoing beyond the threshold value a second time after reaching or goingbeyond the threshold value the first time.

Alternatively or additionally to any of the embodiments above, whereinthe outputted control signal adjusting operation of a cerebrospinalfluid management module is configured to initiate a treatment stopprotocol in response to the value related to the one or moremeasurements of the one or more physiological parameters reaching orgoing beyond the threshold value.

Alternatively or additionally to any of the embodiments above, whereinthe outputted control signal adjusting operation of a cerebrospinalfluid management module is configured to initiate a predeterminedtreatment protocol based on a type of physiological parameter associatedwith the one or more measurements.

Alternatively or additionally to any of the embodiments above, whereinthe outputted control signal adjusting operation of a cerebrospinalfluid management module is configured to initiate a predeterminedtreatment protocol based on the comparison of the value related to theone or more measurements of the one or more physiological parameters tothe threshold value and a type of physiological parameter associatedwith the one or more measurements.

Alternatively or additionally to any of the embodiments above, whereinthe outputted control signal adjusting operation of a cerebrospinalfluid management module causes a cerebrospinal fluid management moduleto initiate a cooling treatment protocol.

Alternatively or additionally to any of the embodiments above, whereinthe outputted control signal adjusting operation of a cerebrospinalfluid management module causes a cerebrospinal fluid management moduleto initiate a filtration treatment protocol.

Alternatively or additionally to any of the embodiments above, whereinthe outputted control signal adjusting operation of a cerebrospinalfluid management module causes a cerebrospinal fluid management moduleto initiate a filtration treatment protocol and a cooling treatmentprotocol.

Another example includes an inflammation management system for managinga patient condition based on values of physiological parameters of apatient. The inflammation system may include a port configured tocommunicate with one or more input devices, the port may be configuredto receive values related to one or more physiological parameters of apatient from the one or more input devices; memory for storing receivedvalues related to the one or more physiological parameters of thepatient; a processor operatively coupled to the port and the memory, theprocessor may be configured to process the received values related tothe one or more physiological parameters of the patient and identifywhen an inflammation condition of the patient reaches a treatmentcondition based on the processed received values related to the one ormore physiological parameters of the patient; and wherein the processorwherein configured to output, via the port, one or more indications thatestablish the inflammation condition of the patient has reached thetreatment condition.

Alternatively or additionally to any of the embodiments above, whereinthe processor may be configured to output a control signal to acerebrospinal fluid management module to perform a treatment oncerebrospinal fluid of the patient in response to identifying when theinflammation condition of the patient reaches the treatment condition.

Alternatively or additionally to any of the embodiments above, theinflammation management system may further comprise: a user interface incommunication with the processor via the port; and wherein the processormay be configured to display a suggested treatment protocol on the userinterface in response to identifying the inflammation condition of thepatient reaches the treatment condition.

Alternatively or additionally to any of the embodiments above, whereinthe processor may be configured to determine an indexed value based onthe received values related to the one or more physiological parametersand identify when the inflammation condition of the patient reaches thetreatment condition based on the indexed value.

Alternatively or additionally to any of the embodiments above, whereinthe received values may relate to two or more physiological parametersand the indexed value may be determined based on the received values forat least two physiological parameters.

Alternatively or additionally to any of the embodiments above, whereinthe indexed value may be a value of a brain inflammation index and thevalues for the at least two physiological parameters may comprise avalue for white blood cell count (WBC), a value for body temperature, avalue for heart rate variability, and a value for photoplethysmography.

Alternatively or additionally to any of the embodiments above, whereinthe indexed value may be a value of a mass effect index and the valuesfor the at least two physiological parameters may include a value for amidline shift from a CT scan, a value for blood volume, a value foredema volume, a value for intracranial pressure, a value for water in abrain of the patient, and a value for brain tissue.

Alternatively or additionally to any of the embodiments above, whereinthe indexed value may be a value of a National Institute of HealthStroke Scale index and the values for the at least two physiologicalparameters may include a value for a level of consciousness, a value ofeye measurements with a pupilometer, a value of motor skills, a value ofsensations, and a value of language skills.

Alternatively or additionally to any of the embodiments above, whereinthe indexed value may be a value of a fluid management index and thevalues for the at least two physiological parameters may include a valuefor a blood pressure, a value for a fluid input and output, a value forcerebral perfusion pressure, a value for sodium content, and a value forpotassium content.

Alternatively or additionally to any of the embodiments above, whereinthe indexed value may be a value of a Glasgow Coma Scale index and thevalues for the at least two physiological parameters may include a valueof eye measurements, a value of motor skills, and a value of languageskills.

Alternatively or additionally to any of the embodiments above, whereinthe indexed value may be based on a plurality of sub-index values.

Alternatively or additionally to any of the embodiments above, whereinthe plurality of sub-index values may include values of two or more of avalue of an inflammation index, a value of a mass effect index, a valueof a National Institute of Health Stroke Scale index, a value of a fluidmanagement index, and value of a Glasgow Coma Scale index.

Alternatively or additionally to any of the embodiments above, whereinthe treatment condition may be a condition related to a subarachnoidhemorrhage of the patient and the indexed value may be based on a valueof an inflammation index, a value of a mass effect index, a value of aNational Institute of Health Stroke Scale index, and a value of a fluidmanagement index.

Alternatively or additionally to any of the embodiments above, whereinthe treatment condition may be a condition related to an intracranialhemorrhage of the patient and the indexed value may be based on a valueof an inflammation index, a value of a mass effect index, and a value ofa National Institute of Health Stroke Scale index.

Alternatively or additionally to any of the embodiments above, whereinthe treatment condition is a condition related to a traumatic braininjury of the patient and the indexed value is based on a value of aninflammation index, a value of a mass effect index, and a value of aGlasgow Coma Scale index.

Alternatively or additionally to any of the embodiments above, whereinthe indexed value may be indicative of a trend for the inflammationcondition of the patient over time.

Another example includes a method of managing inflammation to treat apatient condition, the method comprising: receiving values related tophysiological parameters of a patient; with a processor, processing thevalues related to one or more physiological parameters of the patient;with the processor, identifying an inflammation condition of the patienthas reached a treatment condition based on the processed values relatedto the one or more physiological parameters of the patient; and inresponse to identifying the inflammation condition of the patient hasreached the treatment condition, automatically outputting via a port incommunication with the processor an indication that the inflammationcondition of the patient has reached the treatment condition.

Alternatively or additionally to any of the embodiments above, whereinoutputting the indication that the inflammation condition of the patienthas reached the treatment condition may comprises: outputting a controlsignal from the processor to a cerebrospinal fluid management moduleinstructing the cerebrospinal fluid management module to perform atreatment on cerebrospinal fluid of the patient.

Alternatively or additionally to any of the embodiments above, themethod may further comprise: automatically selecting the treatment fortreating the cerebrospinal fluid of the patient with the processor basedon the processed values related to the physiological parameters of thepatient.

Alternatively or additionally to any of the embodiments above, whereinoutputting the indication that the inflammation condition of the patienthas reached the treatment condition may comprise: displaying on a userinterface a suggested treatment protocol for treatment of theinflammation condition.

Alternatively or additionally to any of the embodiments above, themethod may further comprise: in response to identifying the inflammationcondition of the patient has reached the treatment condition,automatically selecting the suggested treatment protocol from atreatment protocol module with the processor based on the processedvalues related to the one or more physiological parameters of thepatient.

Alternatively or additionally to any of the embodiments above, wherein:processing the values related to the one or more physiologicalparameters of the patient may comprise determining an indexed valuebased on the values related to the one or more physiological parametersof the patient; and identifying the inflammation condition of thepatient has reached the treatment condition may be based on the indexedvalue.

Alternatively or additionally to any of the embodiments above, wherein:the values related to the one or more physiological parameters of thepatient that are received may relate to two or more physiologicalparameters of the patient; and the indexed value may be determined basedon values for at least two physiological parameters.

Alternatively or additionally to any of the embodiments above, whereinthe indexed value may be a value of a brain inflammation index and thevalues for the at least two physiological parameters may comprise avalue for white blood cell count (WBC), a value for body temperature, avalue for heart rate variability, and a value for photoplethysmography.

Alternatively or additionally to any of the embodiments above, whereinthe indexed value may be a value of a mass effect index and the valuesfor the at least two physiological parameters may include a value formidline shift from a CT scan, a value for blood volume, a value foredema volume, a value for intracranial pressure, a value for water in abrain of the patient, and a value for brain tissue.

Alternatively or additionally to any of the embodiments above, whereinthe indexed value may be a value of a National Institute of HealthStroke Scale index and the values for the at least two physiologicalparameters may include a value for a level of consciousness, a value ofeye measurements, a value of motor skills, a value of sensations, and avalue of language skills.

Alternatively or additionally to any of the embodiments above, whereinthe indexed value may be a value of a fluid management index and thevalues for the at least two physiological parameters may include a valuefor a blood pressure, a value for a fluid input and output, a value forcerebral perfusion pressure, a value for sodium content, and a value forpotassium content.

Alternatively or additionally to any of the embodiments above, whereinthe indexed value may be a value of a Glasgow Coma Scale index and thevalues for the at least two physiological parameters may include a valueof eye measurements, a value of motor skills, and a value of languageskills.

Alternatively or additionally to any of the embodiments above, whereindetermining the indexed value may comprise processing a plurality ofsub-index values.

Alternatively or additionally to any of the embodiments above, whereinthe plurality of sub-index values may include values of two or more of avalue of an inflammation index, a value of a mass effect index, a valueof a National Institute of Health Stroke Scale index, a value of a fluidmanagement index, and a value of a Glasgow Coma Scale index.

Alternatively or additionally to any of the embodiments above, whereinthe treatment condition may be a condition related to a subarachnoidhemorrhage of the patient and the indexed value may be based on a valueof an inflammation index, a value of a mass effect index, a value of aNational Institute of Health Stroke Scale index, and a value of a fluidmanagement index.

Alternatively or additionally to any of the embodiments above, whereinthe treatment condition may be a condition related to an intracranialhemorrhage of the patient and the indexed value may be based on a valueof an inflammation index, a value of a mass effect index, and a value ofa National Institute of Health Stroke Scale index.

Alternatively or additionally to any of the embodiments above, whereinthe treatment condition may be a condition related to a traumatic braininjury of the patient and the indexed value may be based on a value ofan inflammation index, a value of a mass effect index, and a value of aGlasgow Coma Scale index.

Another example includes a computer readable medium having storedthereon in a non-transitory state a program code for use by a computingdevice, the program code causing the computing device to execute amethod for managing inflammation to treat a patient conditioncomprising: storing values related to one or more physiologicalparameters of a patient in memory; determining an indexed value based onthe values related to the one or more physiological parameters of thepatient stored in the memory; identifying an inflammation condition ofthe patient has reached a treatment condition based on the indexedvalue; and in response to identifying the inflammation condition of thepatient has reached the treatment condition, automatically outputting anindication that the inflammation condition of the patient has reachedthe treatment condition.

Alternatively or additionally to any of the embodiments above, whereinautomatically outputting the indication that the inflammation conditionof the patient has reached the treatment condition may compriseoutputting a control signal to a cerebrospinal fluid management moduleinstructing the cerebrospinal fluid management module to perform atreatment protocol on cerebrospinal fluid of the patient.

Alternatively or additionally to any of the embodiments above, whereinthe method may further comprise: automatically selecting the treatmentprotocol for treating the cerebrospinal fluid of the patient based onthe indexed value.

Alternatively or additionally to any of the embodiments above, whereinautomatically outputting the indication that the inflammation conditionof the patient has reached the treatment condition may comprisedisplaying on a user interface a suggested treatment protocol fortreatment of the inflammation condition.

Alternatively or additionally to any of the embodiments above, whereinthe method may further comprise: in response to identifying theinflammation condition of the patient has reached the treatmentcondition, automatically selecting the suggested treatment protocol fortreatment of the inflammation condition based on the indexed value.

Alternatively or additionally to any of the embodiments above, whereindetermining the indexed value may comprise processing a plurality ofsub-index values.

Alternatively or additionally to any of the embodiments above, where theplurality of sub-index values may include values of two or more of avalue of an inflammation index, a value of a mass effect index, a valueof a National Institute of Health Stroke Scale index, a value of a fluidmanagement index, and value of a Glasgow Coma Scale index.

Alternatively or additionally to any of the embodiments above, whereinthe indexed value may be indicative of a trend for the inflammationcondition of the patient over time.

Another example includes an inflammation management system for managinga patient condition based on values of physiological parameters of apatient, the system may comprise: a port configured to communicate withone or more input devices, the port is configured to receive valuesrelated to physiological parameters of a patient from the one or moreinput devices; memory for storing received values related to thephysiological parameters of the patient; a processor operatively coupledto the port and the memory, the processor may be configured to processthe received values related to the physiological parameters of thepatient and establish an indexed value indicative of a trend for aninflammation condition of the patient over time based on the receivedvalues related to the physiological parameters; and wherein theprocessor may be configured to output, via the port, an indication basedon the indexed value.

Alternatively or additionally to any of the embodiments above, whereinthe indication based on the indexed value may comprise an indicationthat establishes the inflammation condition of the patient has reached atreatment condition.

Alternatively or additionally to any of the embodiments above, whereinthe indication based on the indexed value may comprise a control signalto a cerebrospinal fluid management module to perform a treatment oncerebrospinal fluid of the patient in response to the inflammationcondition of the patient reaching the treatment condition.

Alternatively or additionally to any of the embodiments above, mayfurther comprise: a user interface in communication with the processorvia the port, the user interface may include a first pane displayingvalues related to the physiological parameters of the patient over timeand a second pane; and wherein the indication based on the indexed valuemay comprises a control signal from the processor to the user interfaceto display the indexed value in the first pane.

Alternatively or additionally to any of the embodiments above, whereinthe indexed value may be displayed in the first pane relative to a rangeof possible indexed values and the values related to the physiologicalparameters of the patient may be displayed in the second pane relativeto a predetermined time period.

The above summary of some embodiments is not intended to describe eachdisclosed embodiment or every implementation of the present disclosure.The Figures, and Detailed Description, which follow, more particularlyexemplify these embodiments.

BRIEF DESCRIPTION OF THE DRAWINGS

The disclosure may be more completely understood in consideration of thefollowing detailed description in connection with the accompanyingdrawings, in which:

FIG. 1 is a schematic depiction of an example inflammation managementsystem in communication with a patient;

FIG. 2 is a schematic block diagram of an inflammation managementsystem;

FIG. 3 is a schematic view of an example display of a user interface ofan inflammation management system;

FIG. 4 is a schematic flow diagram of an inflammation management systemin use with a patient;

FIG. 5 is a schematic flow diagram of an example method of managinginflammation; and

FIG. 6 is a schematic flow diagram of an example method of managinginflammation.

While the disclosure is amenable to various modifications andalternative forms, specifics thereof have been shown by way of examplein the drawings and will be described in detail. It should beunderstood, however, that the intention is not to limit the disclosureto the particular embodiments described. On the contrary, the intentionis to cover all modifications, equivalents, and alternatives fallingwithin the spirit and scope of the disclosure.

DETAIL DESCRIPTION

The incidence of stroke, intracranial hemorrhage, traumatic brain injury(TBI) and subarachnoid hemorrhage result in over 1.1 million hospitaladmissions per year. Acute Ischemic Stroke alone accounts for 700,000admissions per year. Acute brain injury (e.g., caused by trauma,hemorrhage, stroke, etc.) may occur in various degrees and may requirethat the brain go through a healing process.

A patient with an injured brain may deal with fever, seizures, swelling,and/or high intracranial pressure. As discussed below, physicians todayhave limited tools at their disposal to assist in the diagnosing,treating and healing of brain injuries.

Between one-quarter and more than one-half of patients admitted to theneurological intensive care unit (NICU) for acute brain injury develop afever. The cause of fever in these patients often remains unexplained.Central fever related to loss of the physiological regulation of bodytemperature by the hypothalamus is often proposed as a possible causefor persistent fever in patients with acute brain injuries that have noevidence of infection. As hyperthermia is strongly detrimental for therecovery of an acutely injured brain and contributes to an increase inthe length of stay in the NICU, techniques to restore body temperatureto a normal “operating” temperature (e.g., ˜98.6 degrees Fahrenheit (F))play an important role in minimizing inflammation and restoring healingto an injured brain.

Status epilepticus (SE), a condition in which epileptic seizures followone another without recovery of consciousness between the seizures,affects up to 150,000 patients each year in the United States, with amortality between 3% and 33%. Initial treatment of SE with drugs (e.g.,benzodiazepines, phenytoin, and/or phenobarbital) typically fails toterminate SE in 30%-50% of SE cases. The lack of curing SE aftertreatment with drugs may be particularly problematic because cases oflonger duration become more difficult to treat. Even infusions ofanesthetics (e.g., doses of midazolam, pentobarbital, and propofol) thatare traditionally used to control refractory SE, fail in 8%-21% ofcases. Furthermore, seizures, particularly prolonged seizures or seizureepisodes, pose a risk of permanent neuronal damage. Given the incompleteefficacy of current therapies and the potential for neurologic damage,improved diagnoses and earlier treatments need to treat and reduce braininjuries in patient that have SE.

Effective cerebral oxygenation requires an adequate cerebral perfusionpressure and patients suffering an acute brain injury and/or otherconditions may be susceptible to inadequate cerebral perfusionpressures. Cerebral perfusion pressure may depend upon the ‘resistance’offered by intracranial pressure (ICP) or jugular venous pressure (JVP),whichever is higher. Intracranial pressure is determined by the relativeproportion of soft tissue, blood, and CSF within the cranium. Inhealthy, supine adults normal ICP is 5-15 mmHg, becoming sub-atmosphericon standing (around −10 mmHg). Sustained elevations in ICP have beenshown to adversely affect patient outcomes and as such, intracranialhypertension (i.e., elevated ICP) provides a modifiable risk factor inthe management of patients with an acute brain injury or other headinjuries. In most cases, relatively conservative methods such as headelevation, sedation, and/or osmotherapy are sufficient for treatinglower ICP. In over 50,000 cases annually, however, ICP remains elevateddespite the use of these conservative treatment methods.

The disclosed concepts may provide an inflammation management systemthat may diagnose and/or administer therapy in a manner configured toimprove outcomes for patients with acute brain injury. For example, theinflammation management system may be configured to, or may beconfigured to facilitate, an early diagnosis of a condition related toan acute brain injury or other head condition and/or treat the conditionrelated to the acute brain injury or other head condition. In somecases, the inflammation management system may be configured to treatdiagnoses of a patient by conditioning cerebral spinal fluid of thepatient.

Cerebrospinal fluid (CSF) is a generally clear, colorless fluid that isproduced in the ventricles, specifically the choroid plexuses, in thebrain. The choroid plexus produces approximately 500 milliliters of CSFdaily in order to accommodate flushing or recycling of CSF to removetoxins and metabolites, which happens several times per day. From thechoroid plexus, CSF flows slowly through a channel (canal) into thespace surrounding the brain and spinal column, and then into the body.CSF is found in the space between the pia mater and the arachnoid mater,known as the subarachnoid space. CSF is also found in and around theventricular system in the brain, which is continuous with the centralcanal of the spinal cord. In the event of an acute brain injury (e.g., astroke or other brain trauma) or other head injury, it can be desirableto remove the CSF from one location (e.g., the cervical region of thespine, or a brain ventricle), treat (e.g., condition) the removed CSF,and return the removed CSF to the CSF space at the one location and/orat a second location (e.g., the lumbar region of the spine).

Conditioning therapies, such as Neurapheresis™ therapy and/or othersuitable conditioning therapies, may result in the removal of materials(e.g., microrganisms, cells, viruses, foreign material, drugs,combinations thereof, and the like) from CSF. In addition or as analternative to being used to treat conditions related to acute braininjuries (e.g., stroke, TBI, encephalitis, etc.) and/or conditionsrelated to other head injuries, these conditioning therapies and othertherapeutic techniques may be used to treat a number of otherneurological diseases or conditions, such as Alzheimer's Disease,Parkinson's Disease, Huntington's Disease, Amyotrophic Lateral Sclerosis(ALS), Meningitis from various causes, Guillain-Barré Syndrome (GBS),Multiple Sclerosis (MS), HIV-associated neurocognitive disorders, SpinalCord Injury, cerebral vasospasm, and other diseases or conditions.

Purification, conditioning, and/or compound removal schema or systemsare be adjustable to a broad range of physiological parameters andflows. For example, the schema and/or systems can be tailored to aspecific disease or group of diseases as suitable, including based on anumber of features of the disease(s), such as size, affinity,biochemical properties, temperature, and/or other features. Purificationschema may be based on diffusion, size-exclusion, ex-vivo immunotherapyusing immobilized antibodies or antibody fragments,hydrophobic/hydrophilic, anionic/cationic, high/low binding affinity,chelators, anti-bacterial, anti-viral, anti-DNA/RNA/amino acid,enzymatic, and magnetic and/or nanoparticle-based systems.

With regard to an inflammation management system for monitoring apatient (e.g., monitoring a condition of the patient) and/or for use inCSF conditioning therapies (e.g., Neurapheresis™ therapy and/or otherconditioning therapies), the disclosed inflammation management systemcan be used to safely and quickly access the CSF space with minimaldisturbance to the CSF flow in response to diagnosing a condition of apatient. The systems and devices disclosed herein provide a safe andrapid flow circuit.

The inflammation management systems and related devices disclosed hereinmay be used to access the CSF space to remove the CSF from one location(e.g., the cervical region of the spine, or a brain ventricle),condition or otherwise treat the removed CSF, and return the conditionedCSF to the CSF space, including at a second location (e.g., the lumbarregion of the spine), safely and efficiently. In various aspects, theinflammation management system and related devices disclosed herein maymaintain the endogenous ICP or intraspinal pressure within aphysiological range, for example, from about 5 to about 20 mm Hg or fromabout 0 to about 10 mm Hg or from about −5 to about 10 mm Hg or fromabout −5 to about 25 mm Hg.

In various aspects, the inflammation management system and relateddevices disclosed herein may reduce or eliminate recirculating flowloops, which may improve an efficiency of the inflammation managementsystem. In some aspects, the inflammation management system may includesensors within a catheter or within the flow circuit to detect clogs orblockages in the system, thereby providing closed loop pressure control.

In certain aspects, the inlet-outlet spacing of the inflammationmanagement system may be selected to be maximized while staying belowthe level of a cervical region of a patient. Additionally oralternatively, the inflammation management system and related devicesmay maintain spacing between the inlet and outlet, for example, within arange from about 10 cm to about 40 cm. In certain implementations, thespacing is within a range from about 10 cm to about 30 cm.

In certain aspects, the inlet-outlet spacing may be selected based onvertebral spacing. For example, the spacing may be selected so that theinlet-outlet spacing is within a range of lengths from approximatelyfive (5) vertebrae to approximately twelve (12) vertebrae. In certainimplementations, a spacing of approximately 10 vertebrae may beselected; however, other configurations (such as those describedelsewhere in the specification) may be utilized. When designing suchspacing, it may be assumed that a vertebra is approximately 2-3 cm inlength, however, other measurements and designs may be used.

In certain implementations, a particular size, shape, and/or otherconfiguration of a lumen of a catheter for use with the inflammationmanagement system may be selected to facilitate a catheter unblockingand/or the ability of the catheter to resist blockage. For example, aproximal outer diameter of a lumen within a range from approximately0.060 inches to approximately 0.070 inches and a proximal inner diameterwithin a range from approximately 0.025 inches to approximately 0.060inches may be selected; however, other configurations (such as thosedescribed elsewhere in the specification) may be utilized. In someaspects, there may also be multiple holes along an inlet and/or outletof the catheter for redundancy in case there is tissue blocking somenumber of holes. In certain implementations, a particular coil pitch ofa coiled wire within the catheter may be selected in order to reducekinking of the catheter.

The disclosed inflammation management systems and related devices may beused to access the CSF space and may be used at any access point in thecervical (C1-C7), thoracic (T1-T12), or lumbar region (L1-L5) of thevertebral column. An access site in the cervical region may be used toaccess the ventricular system in the brain. In one embodiment, thesystem and device are used to access the lumbar region. In someembodiments, the inlets and outlets of the inflammation managementsystem may be located in places along the spine such that the drainageprocess will not cause tissue to be drawn into the catheter. Forexample, when a patient is lying on a table, entry may be made at asuitable angle, such as, for example, about 90 degrees, to access thespine. A traditional catheter must be pushed through a 90 degree bend atthe L4-L6 region. Components (e.g., catheters and related deliveryand/or other peripheral devices) of the inflammation management systemdisclosed herein may be curved such that they can access and navigatethis angled bend more easily and efficiently.

Turning to the Figures, FIG. 1 schematically depicts an inflammationmanagement system 10 in communication with a patient 14. Theinflammation management system 10 may include or may be configured toconnect to one or more peripheral components 12 that are configured tobe used in conjunction with the patient 14. In some cases, theinflammation management system 10 may include a controller 16, a userinterface 18, one or more communications ports 20, a CSF managementmodule 22 (e.g., a CSF treatment management module including a coolingmodule, a filtration module, and/or other suitable module), acirculation management module 23, and/or one or more other componentssuitable for use in operation of an inflammation management system 10.In some cases, although the circulation management module 23 may beseparate from the controller 16 and the CSF management module 22, asdepicted in FIGS. 1-3, part of or an entirety of the circulationmanagement module 23 may be incorporated into one or both of thecontroller 16 and the CSF management module 22.

Each of the components of the inflammation management system 10 may beconfigured to communicate directly with one another. Alternatively, oneor more of the components of the inflammation management system 10 maybe configured to communicate with another component through thecontroller 16. For example, measurements from the peripheral components12 may be received via the communications port(s) 20 and may be providedto the controller 16. The controller 16 then may interact with the CSFmanagement module 22 to diagnose the patient and/or perform a treatmentusing the CSF management module 22. The controller 16 may interact withthe circulation management module 23 to maintain a predetermined CSFflow rate and/or a CSF fluid pressure below a set point level and/orwithin a range of pressure levels.

The peripheral components 12 may include components used and/orconfigured to facilitate determining diagnoses of and applying therapyto the patient 14 using the inflammation management system 10. Exampleperipheral components 12 include, but are not limited to, catheters,sensors, electrical connectors, mechanical connectors, and/or othercomponents configured to facilitate determining a diagnoses of thepatient 14 and/or applying a therapy to the patient 14 using theinflammation management system 10.

The peripheral components 12 may include an implantable portion and/oran extracorporeal portion. In some cases, one or both of the implantableportion and the extracorporeal portion of the peripheral components 12may have single use functionality and may be disposed after a usethereof, but this is not required.

The implantable portion may contain one or more sensors (e.g.,constituent sensors, pressure sensors, temperature sensors, flowsensors, oxygen sensors, etc.) configured to sense measurements of oneor more physiological parameters of the patient 14 that may be used bythe inflammation management system 10 to control fluid temperature,pressure, and/or other suitable parameters. In one example, theimplantable portion of the peripheral components 12 may include atemperature transducer and a pressure transducer that send signals tothe inflammation management system 10 (e.g., to the controller 16 and/orthe CSF management module 22. The implantable portion of the peripheralcomponents 12 may be placed at one or more locations on the patientincluding, but not limited to between the skull and dura mater, betweenthe dura mater and the brain, within a ventricle, in the subarachnoidspace, and/or at one or more other suitable location. In some cases, theimplantable portion may include a connector that extends to an exteriorof a patient's body when implanted inside the body. Alternatively or inaddition, the implantable portion may be connected to or coupled to thebody of the patient without being implanted inside of the patient'sbody.

The extracorporeal portion may be a suitable component configured toconnect to an input and/or an output of the inflammation managementsystem 10 and connect to the implantable portion, such that theextracorporeal portion may act as an interface between the inflammationmanagement system 10 and the implantable component. The extracorporealportion of the peripheral components 12 may be and/or may include asensor, a catheter, a tube, other elongated component, and/or othersuitable component. Example sensors may be constituent sensors, pressuresensors, flow sensors, temperature sensors, oxygen sensors, and/or othersuitable sensors configured to monitor fluid passing to and/or from theinflammation management system 10. Example catheters may be any suitabletype of catheter configured to transfer fluid to and/or from the patient14 to an inflammation management system 10. Example catheters that maybe used with the inflammation management system 10 are described in U.S.Patent Application Ser. No. 62/286,413 (Attorney docket number1421.1010120) filed on Jun. 18, 2018, and titled “SYSTEMS, CATHETERS,AND METHODS FOR TREATING ALONG THE CENTRAL NERVOUS SYSTEM”, which ishereby incorporated by reference for all purposes. Other suitablecatheters are contemplated.

FIG. 2 schematically depicts illustrative components of the inflammationmanagement system 10. As discussed above with respect to FIG. 1, theinflammation management system 10 may include, among other components,the controller 16, the user interface 18, the communications ports 20,the CSF management module 22, and the circulation management module 23.

The controller 16 may include one or more components. In one example,the controller 16 may include a processor 24, memory 26 in communicationwith the processor 24, input/output (I/O) ports 28 in communication withthe processor 24 and/or the memory 26, and/or one or more other suitablecomponents. In some cases, the memory 26 may be or may includenon-transitory computer readable medium that may include or may beprogrammed to include software and/or other instructions to be executedby the processor 24 and facilitate the controller 16 operating in anautomated manner to output control signals via the I/O ports 28 to theCSF management module 22, to the circulation management module 23, toother components of the inflammation management system 10, and/or toother components usable with the inflammation management system 10 basedon input received at the I/O ports 28 from the CSF management module 22,the user interface 18, and/or communications ports 20 communicating withperipheral components 12. Additionally or alternatively, the controller16 may be configured to receive information from the CSF managementmodule 22 and the circulation management module 23, and/or outputcontrol signals to the peripheral components via the communicationsports 20, the user interface 18, and/or the communications ports 20.

The processor 24 may include a single processor or more than oneprocessor working individually or with one another. Example processorcomponents may include, but are not limited to microprocessors,microcontrollers, multi-core processors, graphical processing units,and/or other suitable processor components.

The memory 26 may include a single memory component or more than onememory component working individually or with one another. Example typesof memory may include RAM, ROM, EEPROM, FLASH, other volatile ornon-volatile memory, or other suitable memory for the controller 16.

The I/O ports 28 may be any type of communication port configured tocommunicate with the CSF management module 22, the circulationmanagement module 23, the user interface 18, the communications ports20, and/or one or more other components of the inflammation managementsystem 10. Example I/O port types may include wired ports, wirelessports, radio frequency (RF) ports, Bluetooth ports, Near-FieldCommunication (NFC) ports, HDMI ports, Ethernet ports, VGA ports, serialports, parallel ports, component video ports, S-video ports, compositeaudio/video ports, DVI ports, USB ports, optical ports, and/or othersuitable ports. Although the I/O ports 28 are depicted as part of thecontroller 16 and separate from the communications port(s) 20, inadditional and/or alternative instances, the I/O ports 28 may be atleast part of the communications port(s) 20 and may be separate from thecontroller 16.

The user interface 18 may be any suitable type of user interfaceconfigured to facilitate a user interacting with the inflammationmanagement system 10. For example, the user interface 18 may include adisplay 30, input/output (I/O) devices 32, and/or other suitable userinterface components configured to facilitate a user interacting withthe inflammation management system 10. The display 30 may include atouch screen and may be an LED, LCD, OLED or other display type. The I/Odevices 32 may include and/or may be incorporated in or with one or moreof a work station, a computer, a computing device, a tablet computer, aphone, a keypad, a display, a touch screen, a touch pad, a mouse, and/orone or more other suitable components that facilitate a user interactingwith the inflammation management system 10.

As depicted in FIG. 3, the display 30 may include any suitable displayconfiguration to facilitate displaying information relating to a patientthat the inflammation management system 10 is monitoring and/ortreating. In some cases, the display 30 may include one or more panes(e.g., where each pane may or may not be separated by visibleboundaries). In one example, the display 30 may include a first pane 30a for displaying one or more medical images of the patient (e.g., anMRI, a CT scan, an x-ray, and/or other suitable medical image of thepatient), a second pane 30 b adjacent to the first pane 30 a thatdisplays measurements of, or values related to measurements of (e.g.,which may be measurements of), and/or indicators related to measurementsof one or more physiological parameters of the patient (e.g.,intracranial hemorrhage (ICH) volume, brain inflammation, white bloodcell count (WBC), body temperature (TMP), heart rate variability (HRV),photoplethysmography (PPG), mass effect on a brain, midline shift (MLS)from a CT scan, blood volume (VOL), edema volume (PHE), intracranialpressure (ICP), water in the brain, brain tissue compliance (CMP),National Institute of Health Stroke Scale (NIHSS), level ofconsciousness (LOC), eye measurements with a pupilometer, motor skills(MTR), sensations (SNS), language skills (LNG), fluid management, bloodpressure (BP), fluid input and output (I/O), cerebral perfusion pressure(CPP), sodium content (Na++), potassium content (K++), and/or othersuitable physiological parameters, an index of physiological parameters(e.g., inflammation index, Glasgow Coma Scale index, NIHSS index, masseffect index, a NEUROWORSENING™ index and/or other suitable indices),etc.), and a third pane 30 c adjacent to the first pane 30 a and/or thesecond pane 30 b that displays patient information (e.g., informationrelated to age, status, premorbid neuro, coagulopathy). The first pane30 a, the second pane 30 b, and/or the third pane 30 c may be updated inreal time in response to incoming data and/or measurements as the dataand/or measurements are received and/or updated at specified orpredetermined intervals. Further, one or more of the first pane 30 a,the second pane 30 b, and the third pane 30 c may be selectable and ifselected, a pane with greater detail may be displayed on the display 30,a date range of the selected pane may be adjusted, and/or the controller16 may cause one or more other suitable changes to what is beingdisplayed on the display 30 and/or how a treatment is being applied.

Additionally or alternatively, the display 30 may include a header 31.The header 31 may be a pane with selectable options for selection tomove between different displays (e.g., a Summary display, an Imagingdisplay, a PHR display, a Trends display, an Analytics display, etc.)

The communications ports 20 may be separate from and/or part of otherI/O ports (e.g., the I/O ports 28 and/or other suitable I/O ports) ofthe inflammation management system 10. The communications ports 20 maybe one or more suitable types of communications ports configured tofacilitate communication between the inflammation management system 10and one or more other components configured to interact with theinflammation management system 10 (e.g., peripheral components 12,etc.). In one example, the communications ports 20 may be configured toconnect to peripheral components 12 (e.g., to receive fluid from apatient and/or to receive measurements and/or data of one or morephysiological parameters of a patient that may be monitored by thecontroller 16 where the measurements and/or data are received fromsensors), connect to scanning equipment, connect to treatmentcomponents, and/or connect to other diagnostic components of and/or incommunication with the inflammation management system 10.

In some instances, the communications ports 20 may be or may includemechanical communications ports and/or electrical communications ports.Example mechanical communications ports may include, but are not limitedto, connection ports configured to facilitate a mechanical connectionbetween the inflammation management system 10 and the peripheralcomponents 12 and/or other suitable components. Such mechanicalcommunications ports may be configured to facilitate fluid being passedto and/or from the CSF management module 22 and/or facilitate electricalsignals being passed to and/or from the inflammation management system10. Example electrical communications ports may be or may include wiredports, wireless ports, radio frequency (RF) ports, Bluetooth ports,Near-Field Communication (NFC) ports, HDMI ports, Ethernet ports, VGAports, serial ports, parallel ports, component video ports, S-videoports, composite audio/video ports, DVI ports, USB ports, optical ports,and/or other suitable ports. In some cases, electrical communicationsports may include a mechanical connection feature.

The CSF management module 22 may include one or more hardware and/orsoftware sub-modules 34. In one example, the CSF management module 22may include a first sub-module 34 a, a second sub-module 34 b, and aN^(th) sub-module 34N, where there are N sub-modules. The hardwareand/or software sub-modules 34 may be swappable or exchangeable to fitdifferent needs, as desired. For example, in one instance, a pump, afiltration treatment module and a waste control mechanism may beutilized for inflammation management; in another instance, a pump and acooling treatment module may be utilized for inflammation management;and in a further instance, a pump, a filtration treatment module, and acooling treatment module may be utilized. Other combinations of hardwareand/or software sub-modules 34 may form or may be part of the CSFmanagement module 22.

The circulation management module 23 may include one or more hardwareand/or software modules (e.g., stored in memory for execution by thecontroller 16 and/or a processor of the circulation management module23) and may be configured to control circulation of CSF through theinflammation management system 10 taking into account protocols of theCSF management module and other circulation requirements. In oneexample, the circulation management module 23 may be configured tomaintain a predetermined CSF flow rate and/or a CSF pressure at or belowa set point level and/or within a range of pressure levels. Thecirculation management module 23 may include a pump 36, but this is notrequired as the circulation management module 23 may rely on other pumpsof the inflammation management system 10 to pump fluid through theinflammation management system 10 according to a circulation protocoltaking into account needs of the CSF management module 22.

In operation, the controller 16 of the inflammation management system 10may interact with a controller of the CSF management module 22 and/orindividual controllers of the hardware and/or software sub-modules 34 toeffect operation of one or more diagnoses and/or treatment protocols. Insome cases, the controller 16 may be configured to interact with thehardware and/or software sub-modules 34 to facilitate control and/oroperation of functionality that may be common to a plurality ofprotocols utilizing the hardware and/or software sub-modules 34. Commonfunctionality that may be controlled and/or performed by the controller16 may include, but is not limited to, real-time and trended pressuremeasurements and recordings, total volume circulated and time elapsedcirculation measurements and recordings, circulation control (e.g., viapressure limiting to prevent pressure from exceeding a set point,maintaining a constant or predetermined flow to deliver circulation at aspecified flow rate, etc.), alarm management, communications, systemstatus updating, and/or other common functionality that may be requiredduring operation of the one or more hardware and/or software sub-modules34. In one example, the controller 16 may be configured to controland/or manage circulation (e.g., by sending control signals to a pump, awaste control mechanism, and/or other hardware and/or softwaresub-module 34) during diagnoses and/or treatment protocols utilizing thehardware and/or software sub-modules 34 (e.g., controlling and/ormanaging fluid circulation and/or pressure monitoring in a controlloop).

The hardware and/or software sub-modules 34 may be configured to buildoff of the base or common functionality provided by the controller 16and provide a specified function during a treatment protocol of apatient. A practitioner or institution may add and/or remove hardwareand/or software sub-modules 34 from the CSF management module 22 totailor the functionality of the CSF management module 22 to a particulardiagnoses and/or treatment protocol, as desired. In one example, whenthe inflammation management system 10 is to be used to diagnose and/ortreat a patient with a head injury, the treating institution and/orpractitioner may install a cooling treatment module. In conjunction withappropriate peripheral components 12, the inflammation management system10 may utilize the base or common functionality thereof (e.g., base orcommon functionality needed by hardware and/or software sub-modules 34,such as circulation management) and the functionality of the coolingtreatment module to cool circulated fluid from a patient according to acooling treatment protocol. In some cases, a cooling treatment protocolmay be saved in software of the cooling treatment module, but this isnot required and the cooling treatment protocol may be saved at anotherlocation and/or inputted to the inflammation management system 10 viathe user interface 18.

In some cases, the CSF management module 22 may be housed in a housingof the inflammation management system 10. Alternatively or in addition,at least part of the CSF management module 22 may be separate from ahousing of the inflammation management system 10. When the CSFmanagement module 22 is housed in a housing of the inflammationmanagement system 10, hardware portions of sub-modules may be swappablefrom the housing in a plug and play manner, but this is not required. Inone example, if a cooling treatment module is needed in a firstconfiguration, but a filtration treatment module is needed in a secondconfiguration, the cooling treatment module may be removed from thehousing of the inflammation management system 10 and replaced with thefiltration treatment module. Further, when the inflammation managementsystem, 10 includes all necessary hardware components, softwaresub-modules 34 may be swapped out and/or exchanged to implement desiredprotocols. Other swappable configurations are contemplated.

FIG. 4 schematically depicts an illustrative configuration of the CSFmanagement module 22 of the inflammation management system 10 in usewith the patient 14 via a peripheral component 12 (e.g., a catheter). Asdiscussed, the CSF management module 22 may include one or more hardwareand/or software sub-modules 34. In the example CSF management module 22depicted in FIG. 4, the hardware and/or software sub-modules 34 includea filtration treatment module 38, a waste control mechanism 40, and acooling treatment module 42. As discussed above, the CSF managementmodule 22 may include one or more additional or alternative hardwareand/or software sub-modules 34 (e.g., up to the N^(th) sub-module).

The pump 36, when included, of the circulation management module 23 maypump or assist in pumping fluid (e.g., CSF or other fluid) into, along,and/or through a fluid circuit of the inflammation management system 10.For example, the pump 36 may pump fluid into an inlet fluid pathway 44,through one or more hardware and/or software sub-modules 34, and out ofan outlet fluid pathway 46. The CSF traveling through the inflammationmanagement system 10 may travel along the fluid circuit through variouspathways via a fluid line 48 having a lumen therein (e.g., tubing orother suitable mechanism forming a lumen and configured to facilitatemaintaining a desired pressure within the fluid circuit by fluid tightconnections at connection points, if any), where the lumen may beconfigured to facilitate travel of CSF along the fluid circuit from aninlet of the fluid line to the pump 36 and from the pump 36 to an outletof the fluid line.

The pump 36 may be configured to pump CSF through the inflammationmanagement system 10 with or without additional pumping mechanisms(e.g., pumps of the other hardware and/or software sub-modules 34 and/orother suitable pumps). Further, although the pump 36 and/or thecirculation management module 23 are depicted and described herein asbeing separate from the CSF management module 22 as a permanentcomponent of the inflammation management system 10, the pump 36 and/orthe circulation management module 23 may be a hardware and/or softwaresub-module 34 of the CSF management module 22.

The pump 36 may be any suitable type of pump for pumping CSF through theinflammation management system 10. For example, the pump 36 may be aperistaltic pump or other suitable pump configured to apply a pressureto a fluid line to pump CSF from a patient, through the inflammationmanagement system 10, and back to the patient. The pump 36 may be asingle pump or multiple pumps configured to achieve a desired pressureand/or flow rate within the fluid line 48. Although the pump 36 islocated upstream of the filtration treatment module 38, the wastecontrol mechanism 40, and the cooling treatment module 42 in FIG. 4, thepump 36 may be located at any suitable location in the inflammationmanagement system 10. In one example, the pump 36 may be locateddownstream of a fluid inlet of the inflammation management system 10 andupstream of a fluid outlet of the inflammation management system 10.

In some cases, the circulation management module 23 may utilize one ormore sensors along a flow path of CSF through the inflammationmanagement system 10 and/or peripheral components 12. The sensors, whenincluded, may be configured to sense a measure within a lumen of thefluid line 48 extending from and/or forming the flow path. Thecirculation management module 23 may take into account, individually orin conjunction with the controller 16, measurements of a single sensor,two sensors, three sensors, or more sensors, as desired, at one or morelocations along the flow path of the inflammation management system 10when controlling circulation of CSF through the fluid line 48 with thepump 36.

The filtration treatment module 38 may include a hardware componentand/or a software component. In one example, if the inflammationmanagement system 10 includes a permanent filtering system, thefiltration treatment module 38 of the CSF management module 22 may be aprimarily software module that utilizes the functionality of thepermanent components (e.g., hardware and software) of the inflammationmanagement system 10 (e.g., the permanent filtering system, thecontroller 16, the user interface 18, the communications ports 20, thefluid line 48 and/or other flow paths, and/or other hardware components)to establish circulation rates (e.g., including, but not limited to,pulsatility) for the filtration treatment module 38 and/or theinflammation management system 10, monitor filtration time, controlevacuation functionality, and/or perform one or more other suitablefunctions using the filtration treatment module 38. Such a softwaremodule may establish a predetermined filtering protocol, which may bemodified by a user via the user interface 18 of the inflammationmanagement system 10 or other user interface and/or may be exchanged forsoftware modules establishing a different predetermined filteringprotocol. The predetermined filtering protocol may be an example of apredetermined treatment or predetermined treatment protocol, among otherexample predetermined treatments or predetermined treatment protocols.

In some cases, the filtration treatment module 38 and/or a permanentfiltering system of the inflammation management system 10 may include ahardware filter system to go along with the software module of thefiltration treatment module 38. In some cases, a hardware filter systemmay include one or more pump components and/or one or more filters.Although other filtration treatment module configurations (e.g., otherhardware and/or software components of the filtration treatment module)are contemplated, an example filtration treatment module is thepump/filtration system for pumping and/or filtering CSF that isdescribed in U.S. Patent Application Ser. No. 62/693,225 (Attorneydocket number 1421.1015100) filed on Jul. 2, 2018, and titled “SYSTEMS,CATHETERS, AND METHODS FOR TREATING ALONG THE CENTRAL NERVOUS SYSTEM”,which is hereby incorporated by reference for all purposes.

In some cases, the hardware components of the filtration treatmentmodule 38 may include one or more filters to filter contaminants (e.g.,blood and/or other contaminants) from CSF. In one example, thefiltration treatment module 38 may have a first filter and a secondfilter. In some instances, one or both of the first filter and thesecond filter may each be a tangential flow filter (TFF) or othersuitable type of filter. For example, the first filter and/or the secondfilter may include a 5 kDa TFF, a 100 kDa TFF, a 0.2 μm TFF, a 0.45 μmTFF, or the like. Alternatively or in addition, the first filter and/orthe second filter may include a dead-end filter (e.g., 5 kDa dead-endfilter) and/or an electrofilter (e.g., a filter that excludes materialsbased on charge).

In at least some instances, the first filter and the second filter, whenboth are included, may be the same size and/or type (e.g., both thefirst filter and the second filter may be 100 kDa TFF). In otherinstances, the first filter and the second filter may differ in sizeand/or type (e.g., the first filter may be a 5 kDa filter and the secondfilter may be a 100 kDa TFF filter).

In some instances, the filtration treatment module 38 may include onlyone filter (e.g., the first filter). For example, the first filter maybe a 5 kDa filter and the first filter may be the only filter.Alternatively, the filtration treatment module 38 may include more thantwo filters (e.g., the first filter, the second filter, and one or moreadditional filters).

The first filter may be configured to separate CSF, when CSF is thereceived fluid, into initial clean CSF (e.g., conditioned CSF) andinitial waste CSF. The initial clean CSF from the first filter may flowto the cooling treatment module 42 and the initial waste CSF from thefirst filter may flow to the second filter.

The second filter, when included, may be configured to separate thereceived initial waste CSF into clean CSF (e.g., conditioned CSF) andwaste CSF (e.g. final waste fluid). The clean CSF from the second filtermay flow to the cooling treatment module 42 and the waste CSF may flowfrom the second filter to the waste control mechanism 40 (e.g., amanually operated or automated (e.g., via a controller) waste pump orother suitable waste control mechanism).

The waste control mechanism 40 (e.g., where the waste control mechanism40 may be or may include a valve, a back pressure valve, a pinch valve,a flow metering mechanism, a pump, etc.) may receive waste fluid via thefluid line 48 from the filtration treatment module 38, as depicted inFIG. 4, and control a rate at which waste CSF is passed along a wasteoutlet pathway to a collection apparatus 50 for disposal (e.g., a rateat which the waste CSF is outputted from the filtration treatment module38). The waste control mechanism 40 may be controlled manually and/or inan automated manner with a controller of the waste control mechanism 40and/or with the controller 16 of the inflammation management system 10.Although other configurations of waste control mechanism 40 arecontemplated, an example waste control mechanism is described in U.S.Patent Application Ser. No. 62/693,225, which was incorporated byreference for all purposes above.

The cooling treatment module 42 may be configured to chill fluid passingthrough the inflammation management system 10 and may include a hardwarecomponent and/or a software component. In some cases, the coolingtreatment module 42 may be configured to receive fluid via the fluidline 48 from the filtration treatment module 38, but this is notrequired, and the cooling treatment module 42 may receive fluid via thefluid line 48 at one or more other locations along the fluid line 48.

The cooling treatment module 42 may include one or more pumps (e.g., inaddition to or as an alternative to the pump 36) and/or one or morevalves to facilitate controlling fluid circulation within the coolingtreatment module 42 and/or otherwise within the inflammation managementsystem 10, but this is not required and fluid circulation may becontrolled by other pumps of the inflammation management system 10. Thepumps and/or valve of the cooling treatment module 42, when included,may be configured to work with the pump 36 and or other pumps of theinflammation management system 10 to control fluid circulation throughthe fluid line 48.

A software component or module of the cooling treatment module 42 mayestablish a cooling protocol for the inflammation management system 10.The cooling protocol may be configured to set temperature set points forfluid passing through the inflammation management system 10 and/or thecooling treatment module 42, set rates at which a temperature of thefluid may be cooled (or, in some cases, warmed), set circulation rates(including, but not limited to, pulsatility) for fluid passing throughthe cooling treatment module 42 and/or the inflammation managementsystem 10, establish hold times for fluids passing through the coolingtreatment module 42 (e.g., a time it takes to reach a temperature setpoint based on ramp rates and circulation rates), and/or perform one ormore other suitable functions using the cooling treatment module 42. Thepredetermined cooling protocol established by the software module of thecooling treatment module 42 may be modified by a user via the userinterface 18 of the inflammation management system 10 or other userinterface and/or may be exchanged for software modules establishing adifferent predetermined cooling protocol. The predetermined coolingprotocol may be an example of a predetermined treatment or predeterminedtreatment protocol, among other example predetermined treatments orpredetermined treatment protocols.

The cooling treatment module 42 may be configured to cool fluid passingthere through in any suitable manner. In some cases, the coolingtreatment module 42 may cool fluid passing there through via radiantcooling and/or other cooling techniques. For example, a surface of thefluid line 48 and/or other fluid pathway of the inflammation managementsystem 10 may be cooled via coils, pre-cooled fluid, and/or cooled inone or more other manners and the cooled surface may remove heat fromthe fluid passing through the cooling treatment module 42 by radiationand/or convection. Alternatively or in addition, the cooling treatmentmodule 42 may cool fluid passing there through by adding a pre-cooledfluid to the fluid passing through the cooling treatment module. In somecases, the added pre-cooled fluid may be a cooled saline, a cooledartificial CSF, and/or other suitable fluid. When adding pre-cooledfluid to the fluid passing through the cooling treatment module 42, anamount (e.g., volume or other amount) of fluid added to the fluidpassing through the cooling treatment module 42 may be determined basedon a function of a volume of material (e.g., fluid or other material)removed from the fluid during filtering of the fluid in order tomaintain a desired balance or ratio fluid inputted to the inflammationmanagement system 10 and fluid outputted from the inflammationmanagement system 10. In one example, a volume of pre-cooled fluid addedto the fluid passing through the cooling treatment module 42 may beequal to or substantially equal to a volume of fluid removed from thefluid passing through the filtration treatment module 38.

In the example depicted in FIG. 4, once fluid passing through the fluidline 48 of the inflammation management system 10 has passed through thefiltration treatment module 38 and the cooling treatment module 42, thefluid may be outputted and returned to the patient. As depicted in FIG.4, the fluid may be returned to the patient 14 at a location that isdifferent than a location at which fluid was removed from the patient14, but this is not required and the fluid that is returned to thepatient 14 may be returned at the same location as or a locationadjacent to the location at which the fluid was removed from the patient14.

As discussed herein, the inflammation management system 10 may be usedin methods of managing inflammation associated with a patient's brain.FIG. 5 depicts an illustrative method 500 of managing inflammation todiagnose and/or treat a patient's condition. Instructions for executingthe method 500 may be stored in memory (e.g., the memory 26 or othersuitable memory) for execution by a processor (e.g., the processor 24, aprocessor of a module or sub-module of the inflammation managementsystem 10, and/or other suitable processor). In some cases, the method500 may be performed entirely or at least partially with an inflammationmanagement system (e.g., the inflammation management system 10 or othersuitable inflammation management system).

As depicted in FIG. 5, the method 500 may include receiving 502 (e.g.,obtaining) one or more values related to physiological parameters of apatient. The one or more values related to physiological parameters ofthe patient may be a measurement of a physiological parameter and/or oneor more other suitable values determined based on the measurement of aphysiological parameter of the patient. The one or more physiologicalparameters of the patient may be received and/or otherwise obtained froma component of the inflammation management system, a peripheralcomponent of the inflammation management system, one or more sensorssensing a physiological parameter of the patient, an image capturingdevice (e.g., a camera, a CT scanning machine, a MM machine, X-raymachine, etc.), and/or other suitable data capturing devices configuredto obtain data related to one or more physiological parameters of thepatient. The one or more values related to physiological parameters ofthe patient may be stored or saved in the memory for access by aprocessor. The values received and/or stored or saved in the memory mayrelate to a single physiological parameter of the patient or two or morephysiological parameters of the patient. In some cases, the one or morevalues related to physiological parameters of the patient may bereceived at the processor for processing from one or more input portsand/or from the memory.

Sensors in or otherwise connected to the inflammation management systemmay provide monitored measurements related to the physiologicalparameters of the patient. Example measurements of physiologicalparameters that may be monitored include, but are not limited to,measurements related to one or more of intracranial hemorrhage (ICH)volume, brain inflammation, white blood cell count (WBC), bodytemperature (TMP), heart rate variability (HRV), photoplethysmography(PPG), mass effect on a brain, midline shift (MLS) from a CT scan, bloodvolume (VOL), edema volume (PHE), intracranial pressure (ICP), water inthe brain, brain tissue compliance (CMP), National Institute of HealthStroke Scale (NIHSS), level of consciousness (LOC), eye measurementswith a pupilometer, motor skills (MTR), sensations (SNS), languageskills (LNG), fluid management, blood pressure (BP), fluid input andoutput (I/O), cerebral perfusion pressure (CPP), sodium content (Na++),potassium content (K++), and/or measurements related to other suitablephysiological parameters.

As values related to physiological parameters of the patient areobtained, those values and/or values related to the physiologicalparameters of the patient stored in the memory may be processed 504. Thevalues related to physiological parameters of the patient may beprocessed using the processor of the inflammation management systemand/or other suitable processor. In some cases, the values related tophysiological parameters of the patient may be processed into one ormore indexed values (e.g., the indexed values may be based on the valuesrelated to the physiological parameters of the patient and are discussedin greater detail below), which may be indicative of an inflammationcondition or other suitable condition of the patient at a current time,indicative of how the inflammation condition has changed overtime,and/or indicative of how the inflammation condition is expected tochange over a future time period. In some cases, the indexed value maybe based, at least in part, on a value or values related to one (e.g., asingle) physiological parameter. Alternatively, the indexed value may bebased, at least in part, on values related to two or more physiologicalparameters.

The inflammation condition of the patient may be a condition of thepatient that is related to a patient condition. The patient conditionmay be or may be related to a traumatic brain injury, a subarachnoidhemorrhage, intracranial hemorrhage, and/or other patient conditioncausing inflammation in, around, and/or affecting a brain of a patientand the inflammation condition may be a level of that inflammation.Typically an inflammation condition of a patient may be difficult toassess or define and use of the processed physiological parameters ofthe patient (e.g., use of indices as discussed herein) may help medicalproviders better understand the inflammation condition of a patientsuffering from a condition causing inflammation in, around, and/oraffecting the patient's brain.

As discussed above, the values related to the one or more physiologicalparameters of the patient may be processed into one or more indices.Each index may have an indexed value, where the indexed value may bebased on measurements of the one or more physiological parameters of thepatient. In some cases, the indexed value may be based on one or moresub-indices and each sub-index of the one or more sub-indices may bebased on measurements of one or more physiological parameters of apatient.

In some cases, the values of one or more physiological parameters for anindex based on values of physiological parameters of a patient may beweighted equally and in other cases, a value of the one or morephysiological parameters for an index may be weighted differently than avalue of one or more other physiological parameters taken into accountfor the index. Similarly, in some cases including an index of one ormore sub-indices, each value of a sub-index used in an index may beweighted equally and in other cases, a value of one or more sub-indicesfor an index may be weighted differently than a value of one or moreother sub-indices taken into account for the index.

An index value may be a value resulting from processing data in aparticular manner for one or more parameters. The indexed value may be avalue resulting from processing data obtained over time for a singleparameter, a value resulting from processing data obtained over time fora plurality of parameters, a value resulting from processing dataobtained at time, t, for a plurality of parameters, and/or othersuitable value. Time, t, is a current time at which data is/wasobtained.

Data for a single parameter may be obtained over time (e.g., from time,t, to a time, t, minus N units of time (time, t−N)) and an indexed valuefor the single parameter may be determined by applying an algorithm tothe obtained data. In one example, an indexed value for data related toa single parameter may be a value of a rolling average of data obtainedfor the single parameter and/or a value resulting from applying one ormore other suitable algorithms to the obtained data for the singleparameter. In another example, an indexed value for data related to aplurality of parameters obtained at time, t, may be a value obtained bynormalizing the data obtained at time, t, for each parameter of theplurality of parameters (e.g., normalizing data for each parameter on ascale from 1-100 or other suitable scale and/or normalizing in one ormore other suitable manners) and taking an average of the normalizedvalue for the parameters of the plurality of parameters and/or a valueresulting from applying one or more other suitable algorithms to theobtained data at time, t, for the plurality of parameters. In anotherexample, an indexed value for data related to a plurality of parametersobtained over time may be a value obtained by normalizing the dataobtained over time for each parameter of the plurality of parameters(e.g., normalizing data for each parameter on a scale from 1-100 orother suitable scale and/or normalizing in one or more other suitablemanners) and taking a rolling average of the normalized value for theparameters of the plurality of parameters and/or a value resulting fromapplying one or more other suitable algorithms to the data obtained overtime for the plurality of parameters. Indices other than those resultingfrom averaging data are contemplated.

The indices based, at least in part, on values related to one or morephysiological parameters a patient may be any suitable index typeincluding, but not limited to, those discussed above. Example indicesinclude, but are not limited to, an inflammation index, a mass effectindex, a NUBS index, a fluid management index, Glasgow Coma Scale index,and/or other suitable indices based, at least in part, on values relatedto one or more physiological parameters of the patient.

The inflammation index may be indicative of brain inflammation (e.g., abrain inflammation index). The inflammation index may be based on, amongother measurements, measurements of one or more of the followingphysiological parameters: white blood cell count (WBC), body temperature(TMP), heart rate variability (HRV), and photoplethysmography (PPG). Inone example, an indexed value may be based, at least in part, on a valueof the inflammation index when the inflammation index is based on avalue for white blood cell count (WBC), a value for body temperature(TMP), a value for heart rate variability (HRV), and a value forphotoplethysmography (PPG)

The mass effect index may be indicative of swelling of the brain. Whenthe mass effect index is above a threshold level, an indication may beprovided to take an action to address swelling of the brain.Alternatively or addition, when the mass effect index reaches thethreshold level, an indication that a symptom related to swelling of thebrain has a particular percentage chance of happening based onhistorical data and/or other suitable information. The mass effect indexmay be based on, among other measurements, measurements of one or moreof the following physiological parameters: midline shift (MLS) from a CTscan, blood volume (VOL), edema volume (PHE), intracranial pressure(ICP), water in the brain, and brain tissue compliance (CMP). In oneexample, an indexed value may be based, at least in part, the masseffect index when the mass effect index is based on a value of themidline shift (MLS) from a CT scan, a value of the blood volume (VOL), avalue of the edema volume (PHE), a value of the intracranial pressure(ICP), a value of an amount of water in the brain, and a value the braintissue compliance (CMP).

The NIHSS index may be indicative of a severity of a stroke. The NIHSSindex may be based on, among other measurements, measurements of one ormore of the following physiological parameters: level of consciousness(LOC), eye measurements with a pupilometer, motor skills (MTR),sensations (SNS), and language skills (LNG). In one example, an indexedvalue may be based, at least in part, on the NIHSS index when the NIHSSindex is based on a value of a level of consciousness (LOC), a value ofeye measurements with a pupilometer, a value associated with motorskills (MTR), a value associated sensations (SNS), and a valueassociated with language skills (LNG).

The fluid management index may be indicative of fluid input into thebody (e.g., fluid input from an IV drip and/or other suitable fluidinput methods) and fluid output from the body (e.g., a fluidconcentration of urine and/or other suitable fluid output methods). Thefluid management index may be based on, among other measurements,measurements of one or more of the following physiological parameters:blood pressure (BP), fluid input and output (I/O), cerebral perfusionpressure (CPP), sodium content (Na++), and potassium content (K++). Inone example, an indexed value may be based, at least in part, on thefluid management index when the fluid management index is based on avalue of blood pressure (BP), a value associated with fluid input andoutput (I/O), a value of cerebral perfusion pressure (CPP), a value ofsodium content (Na++), and a value of potassium content (K++).

The Glasgow Coma Scale index may be indicative of a conscious state of apatient. The Glasgow Coma Scale index may be based on, among othermeasurements, measurements of one or more of the following physiologicalparameters: eye measurements taken with a pupilometer, motor skills(MTR), and language skills (LNG). In one example, an indexed value maybe based, at least in part, on the Glasgow Coma Scale index when theGlasgow Coma Scale index is based on a value of eye measurements takenwith a pupilometer, a value associated with motor skills (MTR), and avalue associated with language skills (LNG).

Other indices based on measurements of physiological parameters of apatient and/or other suitable factors are contemplated. Such otherindices may be based on patient demographics, other suitable factors(e.g., other suitable physiological parameters, etc.), and/or othersuitable combinations of factors.

In some cases, values of the inflammation index, the mass effect index,the NIHSS index, the fluid management index, the Glasgow Coma Scaleindex and/or other suitable indices, may be values of sub-indices thatmay be used or processed to determine a value of an index based on oneor more sub-indices. A value of an index may be a function of one ormore of a value of the inflammation index at a point in time or overtime, a value of the mass effect index at a point of time or over time,a value of the NIHSS index at a point in time or over time, a value ofthe fluid management index at a point in time or over time, and/or avalue of the Glasgow Coma Scale index at a point in time or over time.

An example index of sub-indices may be a NEUROWORSENING™ index. In somecases, the NEUROWORSENING™ index may indicate a patient conditiondeteriorating toward a threshold level prior to actually determining thepatient condition has deteriorated to the threshold level (e.g.,predicting a brain inflammation condition is deteriorating toward athreshold level before being able to diagnose the brain inflammationcondition has reached the threshold level from an image of the patient'sbrain). In one example, the index may be based on one or more differentsub-indices, where the one or more sub-indices may be selected ordetermined depending on a type of patient condition that is beingmonitored and may be indicative of the patient's inflammation condition.For example, when a patient is being monitored due to an intracranialhemorrhage patient condition, an example index of sub-indices may bebased, at least in part, on the inflammation sub-index, the mass effectsub-index, and the NIHSS sub-index; when a patient is being monitoreddue to a subarachnoid hemorrhage patient condition, the index ofsub-indices may be based, at least in part, on the inflammationsub-index, the mass effect sub-index, the fluid management sub-index,and the NIHSS sub-index; and when a patient is being monitored due to atraumatic brain injury patient condition, the index of sub-indices maybe based, at least in part, on the inflammation sub-index, the masseffect sub-index, and the Glasgow Coma Scale index. Other combinationsof sub-indices may be used to develop an index of sub-indices based, atleast in part, on a patient condition for which an inflammationcondition of a patient is being monitored. In some cases, thesub-indices and/or values related to the physiological parameters of thepatient may be selected by individual medical providers to develop anindex for a patient condition, as desired.

In some cases, the sub-indices and/or the index of sub-indices may beindicative of whether the inflammation condition is improving orworsening. In one example, if the values related to the physiologicalparameters of the patient are determined at a current time, the value ofa sub-index may be representative of the patient's inflammationcondition at the current time and when the values related to thephysiological parameters of the patient are saved, the value of thesub-index at the current time may be based on previous values related tothe physiological parameters of the patient and the current valuerelated to the physiological parameters of the patient such that thevalue of the sub-index may be indicative of a trend in the patient'sinflammation condition. Similarly, if the values of the sub-indices aredetermined at a current time, the value of the index of sub-indices maybe representative of the patient's inflammation condition at the currenttime and when the values of the sub-indices are saved, the value of theindex of the sub-indices at the current time may be based on previousvalues of the sub-indices and the current values of the sub-indices suchthat the value of the index of the sub-indices may be indicative of atrend over time of the patient's inflammation condition.

In some cases, the values of the plurality of physiological parametersof the patient, values of the sub-indices of the values of the pluralityof physiological parameters of the patient, and/or the values of theindex of the sub-indices may be depicted or otherwise displayed on auser interface (e.g., the user interface 18 and/or other suitable userinterface). In one example, the values of the plurality of physiologicalparameters of the patient, values of the sub-indices of the values ofthe plurality of physiological parameters of the patient, and/or thevalues of the index of the sub-indices may be depicted on the userinterface with graphs of the values versus time, directional indicatorsindicating whether the respective value is increasing, decreasing, ornot changing from a previous time, ranges where the current value isshown relative to a possible range of values, and/or depicted in one ormore other suitable manners. In some cases, a value of an index ofsub-indices of values related to one or more physiological parameters ofthe patient may be displayed in a first pane of a display of a userinterface relative to a range of possible values for the index ofsub-indices (e.g., the NEUROWORSENING™ index depicted in the second pane30 b in FIG. 3) and values of the sub-indices of the values related toone or more physiological parameters of the patient may be displayed inthe first plane (e.g., the second pane 30 b in FIG. 3) or in a secondpane of the display of the user interface relative to a predeterminedtime period. Displaying such values related to the one or morephysiological parameters of the patient in close proximity to oneanother and/or in close proximity to other information (e.g., patientimages, patient demographic information, etc.) facilitates providing amedical provider with a context for values of the one or morephysiological parameters of the patient that the medical provider wouldtypically not have as such information is typically provided to themedical provider, if at all, via multiple machines and/or printoutsmaking it difficult to understand a context of any individual value orindexed value relative to the patient's condition or inflammationcondition of the patient.

Based, at least in part, on the processed values related to one or morephysiological parameters of the patient, the method 500 may includedetermining 506 whether an inflammation condition of the patient hasreached a treatment condition. In one example, determining 506 whetheran inflammation condition of the patient has reached the treatmentcondition may be based, at least in part, on the indexed valuedetermined during the processing 504 of the values related to the one ormore physiological parameters of the patient.

The treatment condition of the patient may be a level of theinflammation condition of the patient at which a treatment should occurand/or may be indicative of when a treatment should occur. Similar tothe inflammation condition of the patient, the treatment condition ofthe patient may be difficult to assess or define and use of theprocessed physiological parameters of the patient (e.g., use of theindices discussed herein) and associated thresholds or ranges mayfacilitate determining when the inflammation condition of the patienthas reached or will reach the treatment condition. In one example, theprocessed values related to the one or more physiological parameters ofthe patient may result in a value indicative of the patient'sinflammation condition (e.g., an indexed value or other value indicativeof the patient's inflammation condition) and when the value indicativeof the patient's inflammation condition reaches a threshold value (e.g.,a predetermined value, a trend level over time, a value based, at leastin part, on one or more algorithms (e.g., a learning algorithm or othersuitable algorithm) that use data from a plurality inflammationmanagement systems or a global treatment protocol database, and/or othersuitable threshold), it may be determined that the patient'sinflammation condition has reached a treatment condition or will reach atreatment condition at a specifiable time in the future. In some cases,different determinations concerning an inflammation condition relativeto a treatment condition may be made based on a value indicative of thepatient's inflammation condition reaching different thresholds (e.g.,different threshold levels) and/or based on a difference between thevalue and the threshold. When a value of a threshold is based, at leastin part, on an algorithm that uses data from a plurality of inflammationmanagement systems or a global treatment protocol database, the databasemay be a global database storing data from past implementations oftreatment protocols from a plurality of remote inflammation managementsystems (e.g., such data may have information concerning, among otherinformation, what treatment protocol was delivered for a patientcondition, demographic information of the patient, when a treatmentprotocol was performed relative to an inflammation condition, what thevalues of any relevant indices were at the time of implementing ordeciding to implement the treatment protocol, what the values of anyrelevant physiological parameters of the patient were at the time ofimplementing or deciding to implement the treatment protocol, etc.)

When it has been determined that the inflammation condition of thepatient has reached a treatment condition based on the processed valuesrelated to physiological parameters of the patient, an indication thatthe inflammation condition of the patient has reached the treatmentcondition may be outputted 508. In some cases, the indication that theinflammation condition of the patient has reached the treatmentcondition may be outputted from the processor of the inflammationmanagement system or other suitable processor via one or more ports incommunication with the processor (e.g., the I/O ports 32, thecommunications ports 20, and/or other suitable port(s)). The outputting508 of the indication may be performed automatically in response toidentifying the inflammation condition of the patient has reached thetreatment condition, but this is not required in all instances.

The indication that the inflammation condition of the patient hasreached the treatment condition that is outputted 508 may be or mayinclude any suitable indication. Example suitable indications include,but are not limited to, a control signal from the processor to acerebrospinal fluid management module (e.g., a control signal to one ormore sub-modules 34 of the cerebrospinal fluid management module 22 orother suitable components of a cerebrospinal fluid management module) toperform a treatment protocol on cerebrospinal fluid of the patient foraddressing the patient's inflammation condition, a control signal to auser interface (e.g., the user interface 18, a display 30 of the userinterface, and/or other suitable user interface) to display a suggestedtreatment protocol for treatment of the patient's inflammationcondition, a control signal to the user interface to display a value onthe display of the user interface (e.g., a value of an index on a pane,such as the first pane or other suitable pane, of the display), acontrol signal for turning on and/or off a light (e.g., a light of theuser interface or other suitable light), a control signal for turning onand/or off a sound (e.g., from a speaker of the user interface or othersuitable speaker), a control signal initiating an appointment invite orother suitable scheduling mechanism to schedule a medical provider toperform a treatment (e.g., a predetermined treatment and/or othersuitable treatment) at a predetermined time in the future, and/or one ormore other suitable indications.

The treatment protocol may be a set of instructions or list oftreatments for treating the patient's inflammation condition. Exampletreatment protocols may include, but are not limited to, actuation of aCSF filtration treatment, actuation of a CSF cooling treatment,actuation of a CSF drainage treatment, actuation of one or more othersuitable CSF therapies, surgery, etc.

When a treatment protocol is identified, suggested, or obtained, theprocessor may automatically select the treatment protocol based, atleast in part, on processed values related to the physiologicalparameters, a threshold reached, and/or a difference between theprocessed values and a threshold. Such treatment protocols may beautomatically identified or selected by the processor from a database oftreatment protocols associated in a predetermined manner with thevarious patient conditions and values of the processed values related tophysiological parameters of the patient. Alternatively or in addition,treatment protocols may be automatically identified or selected by theprocessor from the database of treatment protocols associated with thevarious patient conditions and values of the processed values related tophysiological parameters based on one or more algorithms (e.g., alearning algorithm or other suitable algorithm). The database may be aglobal database storing data from past implementations of treatmentprotocols from a plurality of remote inflammation management systems(e.g., such data may have information concerning, among otherinformation, what treatment protocol was delivered for a patientcondition, demographic information of the patient, when a treatmentprotocol was performed relative to an inflammation condition, whatvalues of any relevant indices were at the time of implementing ordeciding to implement the treatment protocol, what values of anyrelevant physiological parameters of the patient were at the time ofimplementing or deciding to implement the treatment protocol, etc.) thatis usable by the one or more algorithms to determine associationsbetween treatment protocols and the various patient conditions andprocessed values of the values related to the physiological parametersof the patient that may be relevant to the patient's inflammationcondition.

When it has been determined that the inflammation condition of thepatient has not reached a treatment condition based on the processedvalues related to physiological parameters of the patient (e.g., athreshold or other suitable benchmark has not been reached), theprocessed values related to physiological parameters of the patient maybe monitored 510 and the determining 506 of whether an inflammationcondition of the patient has reached a treatment condition may bedetermined at a future time. In some cases, the steps 502-506 and 510 ofthe method 500 may be repeated and continuously performed at least untilit has been determined the inflammation condition of the patient hasreached the treatment condition. This, however, is not required. In somecases, the one or more steps of the method 500 may be repeated atpredetermined time intervals and/or in response to manual actuation viathe user interface or other suitable user interaction with theinflammation management system.

FIG. 6 depicts an illustrative method 600 of managing inflammation of apatient using an inflammation management system (e.g., the inflammationmanagement system 10 and/or other suitable inflammation managementsystems). Instructions for executing the method 600 may be stored inmemory (e.g., the memory 26 and/or other suitable memory) for executionby a processor (e.g., the processor 24, a processor of a module orsub-module of the inflammation management system 10, and/or othersuitable processor).

Initially, although not required, a patient (e.g., the patient 14 orother suitable patient) may be connected to the inflammation managementsystem via one or more peripheral components (e.g., the peripheralcomponents 12 or other suitable peripheral components). Once the patienthas been connected to the inflammation management system, theinflammation management system may monitor 602 measurements or valuesrelated to measurements of one or more physiological parameters of apatient over time on which CSF drainage, CSF cooling, CSF filtration,and/or other CSF therapies may be based. In operation, the monitoring602 may be performed by a controller (e.g., the controller 16 or othersuitable controller) of the inflammation management system.

The method 600 may include comparing 604 a value related to themonitored measurements of the one or more physiological parameters ofthe patient (e.g., an indexed value as discussed above with respect toFIG. 5 and/or other suitable value related to the one or morephysiological parameters of the patient) to one or more threshold values(e.g., a threshold value determined in the manner discussed above withrespect to FIG. 5 and/or determined in one or more other suitablemanners). In one example, comparing 604 a value related to the monitoredmeasurements of the one or more physiological parameters of the patientto one or more threshold values may include determining a differencebetween the value related to the monitored measurements of the one ormore physiological parameters and the threshold value, but this is notrequired. In operation, the comparing 604 may be performed by thecontroller of the inflammation management system and/or other suitablecontroller.

Then, based on the comparison of the value related to the monitoredmeasurements of the one or more physiological parameters to thethreshold value, the method 600 may include adjusting 606 operation of aCSF management module (e.g., the CSF management module 22 and/or othersuitable CSF management module). For example, if the value related tothe monitored measurements of the one or more physiological parametersreaches or goes beyond a threshold value, operation of the CSFmanagement module 22 may be adjusted (e.g., via a control signal) toinitiate a filtration protocol using a filtration treatment module(e.g., the filtration treatment module 38 and/or other suitablefiltration treatment module), a cooling protocol using a coolingtreatment module (e.g., the cooling treatment module 42 and/or othersuitable cooling treatment module), and/or other suitable treatmentprotocol (e.g., other suitable predetermined or learned/developedtreatment protocols) using a sub-module (e.g., the hardware and/orsoftware sub-modules 34 or other suitable sub-modules) of the CSFmanagement module. In an additional or alternative example, when adifference between the value related to the monitored measurements ofthe one or more physiological parameters and the threshold value isdetermined, the operation of the CSF management module may be adjustedbased on the determined difference between the value related to themonitored measurements of the one or more physiological parameters andthe threshold value. Alternatively or in addition, operation of the CSFmanagement module may be adjusted based on one or more additional oralternative factors.

Adjusting 606 the operation of the CSF management module may beautomatically executed according to a treatment protocol (e.g.,initiating: a treatment start protocol (e.g., which initiates othertreatment protocols), a treatment stop protocol (e.g., which stops othertreatment protocols), a filtration treatment protocol, a coolingtreatment protocol, a suitable predetermined treatment protocol (e.g.,which may or may not include the treatment start protocol, the treatmentstop protocol, the filtration treatment protocol, the cooling treatmentprotocol and/or other suitable predetermined treatment protocols),and/or other suitable treatment protocols) of the CSF management modulebased on the comparison of the value related to the monitoredmeasurements of the one or more physiological parameters to thethreshold value. In some cases, a treatment start protocol may bestarted in response to determining the value related to the monitoredmeasurements of the one or more physiological parameters reaches or goesbeyond the threshold value a first time and a treatment stop protocolmay be started in response to determining the value related to themonitored measurements of the one or more physiological parametersreaches or goes beyond the threshold value a second time after reachingor going beyond the threshold value the first time. Further, a type oftreatment protocol (e.g., a type of predetermined treatment protocol,such as the cooling treatment protocol, the filtration treatmentprotocol, and/or other therapy or treatment protocols, and/or a type ofnon-predetermined treatment protocols (e.g., learned and/or developedtreatment protocols)) may be automatically selected by the controller(s)of the inflammation management system based on a type or types ofphysiological parameters associated with the monitored measurementshaving a related value that reaches or goes beyond a threshold valueand/or a value of a determined difference between the value related tothe monitored measurements of the one or more physiological parametersand the threshold value and/or selected in the manner discussed abovewith respect to FIG. 5.

The automatic execution of the adjustments to the operation of the CSFmanagement module may be effected using one or more controllers of theCSF management module and/or the controller(s) of the inflammationmanagement system to treat and/or diagnose brain injuries. As analternative to the automatic execution of the adjustments to theoperation of the CSF management module, an alarm or other notificationmay be issued (e.g., via email, via a noise warning, a light warning, anindication on a user interface (e.g., the user interface 18 and/or othersuitable user interface)), and a user may manually adjust operation ofthe CSF management module and/or manually initiate an adjustment of anoperation of the CSF management module.

In addition to or as an alternative to adjusting an operation of the CSFmanagement module (e.g., the circulation management module 23 and/orother suitable circulation management modules) in response to the valuerelated to the monitored measurements of the one or more physiologicalparameters reaching or going beyond a threshold value, the controller 16may adjust operation of the circulation management module to activelydrain CSF from a patient. In some cases, the operation of thecirculation management module to actively drain CSF form the patient mayoccur while adjusting operation of the cooling treatment module to coolCSF for a predetermined amount of time, adjusting operation of thefiltration treatment module to filter CSF at a predetermined flow rate,and/or adjusting operation of the CSF management module in one or moreother manners.

The inflammation management system 10 may be used to treat a number ofconditions. Some of the contemplated conditions include cancer. Forexample, Leptomeningeal Metastases (LM) is a condition in which cellsfrom a primary solid or hematological tumor metastasize, invade thesubarachnoid space (SAS), and spread throughout the cerebrospinal fluid(CSF), resulting in seeding of the leptomeninges along the surface ofthe central nervous system (CNS). LM represents a late event of cancerprogression and the most frequent symptoms include multiple cranialnerve deficits, motor deficits, altered mental status, headache, andradicular pain. The incidence of LM is estimated at 3-5% of cancerpatients and has been increasing, due to longer overall survival incancer patients. LM presents a difficult challenge in metastatic cancertreatment plans, resulting in a devastating prognosis and mediansurvival of 4 months because of lack of effective access and therapies.Systemic therapy with anti-cancer drugs including methotrexate (MTX),cytarabine and thiotepa are not as effective due to poor penetration ofthe blood-brain barrier (BBB). Intrathecal (IT) drug delivery systems,including Ommaya reservoirs, have been associated with longer overallsurvival; however, they require repeated injections and rely on passivediffusion. Future therapies that target the entire CNS and enhance thedistribution of IT drugs could further improve survival. CSF is producedat approximately 20 ml/hr, with a total volume of ˜150 ml, resulting ina turnover, on average, of three times per day. The production rate ofCSF is independent of intracranial pressure (ICP). As LM can block theoutflow paths of CSF, patients are at serious risk of hydrocephalus andelevated ICP. Additionally, the relative isolation of the CSF by the BBBand blood-CSF barriers, presents a unique environment for tumorsurvival.

The inflammation management system 10 may have the ability to rapidlyclear a number of CSF pathogens and cells, as well as to enhance drugdelivery in the CSF. For example, the inflammation management system 10may be used to improve the LM outcome by 1) enhanced exposure andcirculation of specific anticancer agents (MTX delivered through anOmmaya reservoir, a catheter, or both) throughout the SAS, (2) localfiltering of CSF to remove cancer-spreading circulating tumor cells(CTCs), (3) control of ICP via CSF drainage, (4) filtration of tumorcells (e.g., living and/or dead tumor cells that may clog the naturalreabsorption of the CSF via the arachnoid granulations and lymphaticsystem The inflammation management system 10 may also be used to reducethe concentration of a drug (e.g., a chemotherapy agent such asmethotrexate) in the CSF (e.g., in order to remove excess drug, reducetoxicity, etc.).

As alluded to herein, treatment methods are contemplated that includeinfusing a chemotherapy agent into the patient. In some instances, thechemotherapy agent is methotrexate. Other chemotherapy agents arecontemplated. The chemotherapy agent may be infused into the CNS via anOmmaya reservoir (and/or or a similar device including, for example, aRickham device) implanted in the ventricles of the patient, as isstandard of care in these patients. In addition or in the alternative,the chemotherapy agent may be infused into the patient using a catheter.For example, the chemotherapy agent may be added to a clean CSF outletpathway, to one of the ports of the catheter, via a separate devicedisposed adjacent to the catheter, or in another suitable manner. Thecirculation of CSF by the inflammation management system 10 may help tocirculate the chemotherapy agent throughout the cerebrospinal spaceand/or the CNS.

Another contemplated condition that the inflammation management system10 may be used to treat is Amyotrophic Lateral Sclerosis (ALS). Forexample, the pathology of ALS may be correlated with overstimulation ofglutamatergic functions/pathways with a corresponding excitotoxicity,increased calcium levels, and/or the generation of reactive oxygenspecies. Oxidative stress may be involved in pathological mechanisms ofALS via cell death-related release of pro-oxidative compounds andredox-active iron, mitochondrial dysfunction, inflammation, andexcitotoxicity. The inflammation management system 10 may be used tohelp reduce/clear the CSF of oxidative and/or inflammatory agents (e.g.,including free radicals, cytokines, chemokines, white blood cells) suchas those correlated with the pathology of ALS. Some examples ofmaterials that may be reduced/removed as part of treating ALS mayinclude one or more of insoluble superoxide dismutase-1 (SOD1),glutamate, neurofilament protein, and anti-GM1 ganglioside antibodies.

In some instances, the oxidative and/or inflammatory agents may carry anelectrical charge. Removal of such materials may be enhanced utilizingelectrofiltration (e.g., a filter having an electrical charge).Accordingly, in at least some instances, the first filter, the secondfilter, both, and/or one or more other filter may include anelectrically charged filter (electrofilter). In some of these and inother instances, the first filter, the second filter, or both mayinclude an immunoaffinity column, a size exclusion column, an anionicexchange column, a cationic exchange column, and a Protein A or ProteinG column.

In addition to removing CSF-borne pathological mediators correlated withALS, the inflammation management system 10 may also be used to deliverone or more drugs to the CSF. Such treatments may help further reduceoxidative and/or inflammatory agents. In some instances, the drug may beadded to the clean CSF outlet pathway (e.g., the return outlet), to oneof the ports of the catheter, via a separate device disposed agent tothe catheter, or in another suitable manner. The circulation of CSF bythe inflammation management system 10 may help to circulate the drugthroughout the cerebrospinal space and/or the CNS. Some example drugsthat may be utilized may include riluzole, edaravone, or the like.

Another contemplated condition that the inflammation management system10 may be used to treat is herpes simplex encephalitis (HSE). HSE isknown to cause severe neuroinflammation, cerebral edema and hemorrhagicnecrosis with resultant increases in intracranial pressure (ICP). Whilemedical management has been standardized, aggressive combined medicaland surgical management including decompressive craniectomy and/ortemporal lobectomy is often performed due to uncontrolled ICP,neuroinflammation and cerebral edema. The production of reactive oxygenspecies (ROS) are also believed to be a component of natural defenses toviral infection. However, the lipid-rich environment of the CNS may besusceptible to oxidative damage. Thus, oxidative damage can becorrelated with HSE infection.

The inflammation management system 10 may be used to remove oxidativeand/or inflammatory agents (e.g., including free radicals, cytokines,chemokines, white blood cells) such as those correlated with thepathology of HSE. In some instances, the oxidative and/or inflammatoryagents may carry an electrical charge. Removal of such materials may beenhanced utilizing electrofiltration (e.g., a filter having anelectrical charge). Accordingly, in at least some instances, the firstfilter, the second filter, or both may include an electrically chargedfilter (electrofilter).

Another contemplated condition that the inflammation management system10 may be used to treat is human immunodeficiency virus (HIV) and/oracquired immune deficiency system (AIDS). HIV infection of the CNS canlead to a number of complications including meningitis, acuteinflammatory polyneuropathy (AIDP), immune reconstitution inflammatorysyndrome (IRIS)—initiated by introduction of antiretroviral therapy,chronic inflammatory polyneuropathy (CIDP), distal symmetricpolyneuropathy (DSP), progressive multifocal leuko-encephalopathy (PML),and HIV-associated neurocognitive disorders (HAND). The inflammationmanagement system 10 may be designed to filter/reduce/remove a number ofdifferent strains of HIV from the CNS. This can reduce viral load in theCSF and/or reduce complications associated with HIV infection in theCNS. In addition, the inflammation management system 10 may be designedto filter/reduce/remove a number of different inflammatory agentsassociated with HIV from the CNS.

Another contemplated condition that the inflammation management system10 may be used to treat is multiple sclerosis (MS). Two subtypes,Clinically Isolated Syndrome (CIS) and Relapsing-Remitting MultipleSclerosis (RRMS), represent the disease absent progression, whilePrimary Progressive (PPMS) and Secondary Progressive (SPMS) representpatients with progressive disease from the start or after RRMS,respectively. Neuroinflammation leading to multifocal lesion formation,demyelination, axonal damage and consequent neurodegeneration arehallmarks of the disease. Current treatments may be classified asincluding (1) anti-inflammatory naturally-occurring molecules(IFN-beta), (2) molecules that stimulate anti-inflammatory (glatirameracetate) or inhibit autoreactive (teriflunomide) cell proliferation, (3)immunosuppressive monoclonal antibodies (natalizumab), (4) moleculesthat bind transcription factors to enhance anti-inflammatory mechanismsor suppress pro-inflammatory ones (dimethyl fumarate), and (5) agentsthat inhibit egress of lymphocytes from lymphoid tissue to the CNS(fingolomod). In some instances, the inflammation management system 10may be designed to filter/reduce/remove a number of differentinflammatory agents associated with MS including immune cells(immunoglobins, neutrophils, lymphocytes, monocytes, and the like),oxidative and/or inflammatory agents (e.g., including free radicals,cytokines, chemokines, white blood cells) such as those correlated withthe pathology of MS, and the like. This can help treat MS and/or improvethe symptoms thereof.

Another contemplated condition that the inflammation management system10 may be used to treat is Guillain-Barré syndrome (GBS). GBS is themost common cause of acute paralytic neuropathy worldwide. Acute motoraxonal neuropathy (AMAN) and acute inflammatory demyelinatingpolyneuropathy (AIDP) are the main phenotypes. GBS may arise inindividuals through a combination of host genetic and environmentalfactors, and preceding infection by pathogens including Campylobacterjejuni and Zika virus. Prevailing mechanisms of action implicatemolecular mimicry of foreign antigen and gangliosidic residues resultingin the development of autoantibodies which recognize myelin or axonalcomponents and initiate an inflammatory immune response includingmacrophage and/or lymphocytic infiltration, complement deposition, andcytokine production. CSF analysis shows elevated protein (>400 mg/L) andthe absence of pleocytosis in 90% of patients. Elevated levels ofneuroinflammatory cytokines and other proteins involved in the pathologyhave been noted, though specific immunological protein profiles of GBSCSF are heterogenous. In some of these and in other instances, a secondcatheter may be used to infuse a drug into the cranial region.

Current treatments for GB S may include plasma exchange (PE) orintravenous immunoglobulins (IVIg) with supportive care. Based onprotein abnormalities of the CSF in GBS patients, including elevatedlevels of inflammatory cytokines TNF-α and IL-6⁷, anti-gangliosideantibodies, and activated complement components, filtration of CSF toreduce/remove inflammatory may help to reduce GBS systems and/or treatGBS. In some instances, The inflammation management system 10 may bedesigned to filter/reduce/remove a number of different inflammatoryagents associated with GBS including immune cells (immunoglobins,neutrophils, lymphocytes, monocytes, and the like), oxidative and/orinflammatory agents (e.g., including free radicals, cytokines,chemokines, white blood cells) such as those correlated with thepathology of GBS, and the like. This can help treat GBS and/or improvethe symptoms thereof. In some instances, the inflammation managementsystem 10 may include a 5 kDa filter when used for treating GBS. Otherfilter sizes are contemplated including those disclosed herein. Forexample, the inflammation management system 10 may include a 5 kDatangential flow filter, a 100 kDa tangential flow filter, anelectrofilter, or a combination thereof.

Another contemplated condition that the inflammation management system10 may be used to treat is meningitis. Bacterial meningitis occurs whenpathogenic bacteria enter the subarachnoid space and cause a pyogenicinflammatory response. Gram-negative bacterial meningitis (GBM) is adevastating condition that occurs when gram-negative bacteria invade thecentral nervous system (CNS). There are 30,000 US cases and over 1million cases of GBM worldwide annually. When bacterial infections aremanifested as GBM, it creates an extreme burden of mortality, oftenexceeding 30%, and morbidity to the patient and is very difficult forclinicians to treat, even when caused by bacteria susceptible tostandard antibiotics. It is seen most commonly in children orimmunocompromised patients, such as those with HIV, postorgan-transplant or post-neurosurgical procedures. Current treatmentguidelines include intravenous cephalosporins or carbapenems orpolymycin for at least 10 days to 2 weeks. In the presence ofgram-negative enteric bacterial meningitis, classically occurring aroundtrauma and neurosurgical procedures, highly resistant bacteria can causedisease. Antibiotics like aminoglycosides and polymycins are consideredfor treatment but the therapeutic-toxic ratio is poor for these agentswith systemic use in CNS disease and there may be no optimal treatments.

Three key gram-negative pathogens that have been deemed criticalpriority include Pseudomonas, Acinetobacter and Klebsiella (PAK). Thesegram-negative bacteria can cause severe and often deadly infections suchas pneumonia, bloodstream infections and, specifically, nosocomialmeningitis. These bacteria have become resistant to a large number ofantibiotics, including carbapenems and third generationcephalosporins—the best available antibiotics for treatingmultidrug-resistant bacterial meningitis. The world health organizationacknowledges that multi-modal approaches are needed and that waiting anylonger will cause further public health problems and dramatically impactpatient care and survival. This raises the very real possibility of GBMinfections that are untreatable by presently available antibiotics. Thisreturn to the pre-antibiotic era has unfortunately become a reality inmany parts of the world.

Reduction in CSF organism burden is the single most important factorimpacting survival and is linked to a better overall clinical outcome.The rapid reduction in CSF organism burden is important, withsterilization of the CSF in the first 24 hours. Optimization of theantibiotic effect depends directly on the organism load that is presentand on the direct activity of antibiotic therapy being started early ininfection. Determining which antibiotic agent will be most effective isbecoming increasingly more difficult in the face of drug-resistantbacteria such as PAK. Clinical data for new antibiotics for bacterialmeningitis simply have not kept pace with the rise of resistance, andthe development of new therapeutic approaches is urgently needed.Additionally, experimental animal models have shown that outcome frombacterial meningitis are related to the severity of inflammation in thesubarachnoid space (SAS) and could potentially be improved by modulationof the inflammatory response.

The inflammation management system 10 may provide an innovative newtreatment option that provides direct access to the CSF and createsactive circulation combined with targeted pathogen removal. This mayprovide a novel therapeutic approach that rapidly reduces CFUs and CSFbacterial burden and translates to reduced morbidity and mortality frombacterial meningitis.

Accordingly, the present methods provide for ameliorating or reducingthe symptoms of bacterial meningitis by reducing or eliminating thepresence of one or more of bacterial pathogens and/or their associatedendotoxins and/or cytokines in the CSF using the inflammation managementsystem 10. The methods comprise removing CSF from a patient, removing atleast one of the bacterial pathogens, and/or endotoxins associated withthe bacterial pathogens, and/or cytokines from the CSF, and returningthe endogenous CSF to the patient, wherein the removing and returningsteps are performed concurrently during at least a portion of thetreatment. In some embodiments, the cytokines are selected from thegroup consisting of IL-1ra, IL-6, TNF, CRP, and CXCL10, or combinationsthereof.

In some of these and in other instances, the methods provide forameliorating or reducing the symptoms of bacterial meningitis byintroducing a catheter through a spinal access site into a spinal CSFspace of a patient, advancing the catheter through the spinal CSF spacetoward the brain so that openings of the catheter are disposed withinthe CSF space and spaced-apart by a preselected distance or adjusted toan appropriate distance, withdrawing CSF through at least some of theopenings in the catheter, removing at least one of bacterial pathogensand/or their associated endotoxins and/or cytokines from the withdrawnCSF with the inflammation management system 10 (thereby conditioning theCSF), and returning the conditioned CSF through the other of theopenings in the catheter.

Fungal meningitis (FM) is an infection of the meninges of the centralnervous system that manifests from the dissemination of any major fungalpathogen into the subarachnoid space (SAS) via the cerebrospinal fluid(CSF). Cryptococcal Meningitis (CM) is caused by Cryptococcus neoformansand is the most common cause of fungal meningitis in adults. Otheragents causative of fungal meningitis include: C. Gattii, Blastomyces,Histoplasma, Coccidioides. Treatment for CM is based on an induction,consolidation, and maintenance approach with antifungals and is welldefined elsewhere, but is associated with continued high morbidity andmortality. Drug discovery programs are limited by poor penetration ofthe Blood Brain Barrier (BBB). Because of this, we developed analternative catheter-based extracorporeal filtration system(Neurapheresis Therapy) for the filtration of infected CSF. Here wedescribe the in vitro characterization of Neurapheresis Therapy as analternative mechanical intervention for filtration of C. neoformanscells, polysaccharide antigen, and inflammatory mediators from infectedCSF.

The inflammation management system 10 may provide an innovative newtreatment option that provides direct access to the CSF and createsactive circulation combined with targeted pathogen removal. This mayprovide a novel therapeutic approach that rapidly reduces CFUs and CSFfungal burden and translates to reduced morbidity and mortality fromfungal meningitis. In at least some instances, the inflammationmanagement system 10 may include one or more filters designed to excludethe passage of fungi therethrough such as C. neoformans. In some ofthese and in other instances, the inflammation management system 10 mayinclude one or more filters designed to exclude fungi (e.g., C.neoformans), associated antigens, and/or inflammatory agents. In atleast some instances, a single pass of CSF through a 5 kDa TFF and/or a100 kDa TFF may be sufficient to exclude C. neoformans or other reducethe CFUs of C. neoformans in the CSF. In addition, a 5 kDa TFF and/or a100 kDa TFF may be sufficient to exclude or otherwise reduce C.neoformans antigen from the CSF. Furthermore, a 5 kDa and/or 100 kDa TFFmay also exclude a number of neuroinflammatory agents such as IL-1ra,IL-6, TNF, CRP, and/or CXCL 10/IP-10 from the CSF.

Accordingly, the present methods provide for ameliorating or reducingthe symptoms of fungal meningitis by reducing or eliminating thepresence of one or more of fungal pathogens and/or their associatedantigens (e.g., Cryptococcal antigen) and/or cytokines in the CSF usingthe inflammation management system 10. The methods comprise removing CSFfrom a patient, as described herein; removing at least one of the fungalpathogens, and/or antigens associated with the fungal pathogens, and/orcytokines from the CSF, and returning the endogenous CSF to the patient,wherein the removing and returning steps are performed concurrentlyduring at least a portion of the treatment. In some embodiments, thecytokines are selected from the group consisting of IL-1ra, IL-6, TNF,CRP, and CXCL10, or combinations thereof. The fungus/fungi and/orantigens and/or cytokines can be removed from the CSF using one or morefiltration system. A 5 kDa and/or 100 kDa TFF may also exclude a numberof neuroinflammatory agents such as IL-1ra, IL-6, TNF, CRP, and/or CXCL10/IP-10.

In some of these and in other instances, the methods provide forameliorating or reducing the symptoms of fungal meningitis byintroducing the catheter through a spinal access site into a spinal CSFspace of a patient, advancing the catheter through the spinal CSF spacetoward the brain so that the openings of the catheter are disposedwithin the CSF space and spaced-apart by a preselected distance oradjusted to an appropriate distance, withdrawing CSF through at leastsome of the openings in the catheter, removing at least one of fungalpathogens and/or their associated antigens and/or cytokines from thewithdrawn CSF with the inflammation management system 10 (therebyconditioning the CSF), and returning the conditioned CSF through theother of the openings in the catheter.

In at least some instances, the inflammation management system 10 may beused to deliver drugs to portions of the CNS. For example, sometreatments for CM may include the administration of intravenous and oralantifungals such as amphotericin B (AmB) and flucytosine. Generally,intrathecal (IT) AmB boluses may be associated with neurotoxic drugconcentrations near the injection site. The use of the inflammationmanagement system 10 may allow for the IT infusion of AmB and/or otherdrugs. Unexpectedly, the inflammation management system 10 may also beused to reduce, filter, or otherwise remove some drugs such as AmB.Because of this, the dosage of AmB can be precisely titrated to adesired dose. If levels of AmB reach undesired levels (e.g., undesiredhigh levels), the inflammation management system 10 can be used toquickly remove unwanted quantities of AmB from the CSF.

The inflammation management system 10 can also be used to deliver anumber of other drugs including drugs where the difference betweentherapeutic doses and toxic doses are relatively small. For example, adrug may be infused into the CSF using the inflammation managementsystem 10. If signs of toxicity are observed or if measurements of thedrug concentration in the CSF is higher than desired, the inflammationmanagement system 10 can be used to rapidly remove the drug from theCSF. Thus, the inflammation management system 10 can be used forcontrolled delivery of drugs into the CSF of patients and the rapidremoval of drugs from the CSF, as desired.

The inflammation management system 10 may also help to reduce ICPassociated with a number of conditions. For example, some conditions(e.g., such as cancer, HSE, and others) may be associated with higherICP due to cells (e.g., tumor cells, etc.), inflammatory agents, and thelike blocking, clogging, or otherwise impacting natural pathways forreabsorption of CSF. By using the inflammation management system 10,materials that might blocking natural reabsorption pathways can beremoved/reduced, thereby desirably impacting the volume of CSF andreducing ICP.

Systems are also contemplated that utilize a first port for providingaccess to the cerebrospinal space and/or the CNS at a first location anda second port for providing access the cerebrospinal space and/or theCNS at a second location. Such ports may be implanted acutely or forextended periods of time. In some instances, the ports may allow forinfusion of substances to the cerebrospinal space and/or the CNS,removal of substances from the cerebrospinal space and/or the CNS, orboth. One or both of the ports may be or otherwise be similar to anOmmaya reservoir. The ports may be designed to be used with atube/catheter, the inflammation management system 10. For example, afirst tube and/or first catheter may be connected with or otherwise beconnectable to one of the ports and a second tube and/or second cathetermay be connected with or otherwise be connectable to the other port. CSFmay be removed from the patient (e.g., using a tube, either the first orthe second catheter, or the like) and filtered by the inflammationmanagement system 10. In some instances, the filtered CSF may bereturned to the patient using the same tube/catheter. In otherinstances, the filtered CSF may be returned to the patient using theother tube/catheter. In other words, CSF may be removed from the patientusing a catheter at the first port, filtered, and then returned to thepatient using a catheter at the second port. This may form a loop-likepathway the helps to circulate CSF through the cerebrospinal spaceand/or the CNS. The ports may be positioned along the patient in amanner that helps to facilitate circulation of CSF. For example, one ofthe ports may be positioned at the cranium of the patient (e.g., whichmay include providing access to the ventricles of the brain) and theother may be positioned along a lumbar region of the spine (e.g., whichmay provide access to the cerebrospinal space at a position adjacent tothe lumbar space). Other locations are contemplated.

All directional references (e.g., proximal, distal, upper, lower,upward, downward, left, right, lateral, front, back, top, bottom, above,below, vertical, horizontal, clockwise, and counterclockwise) are onlyused for identification purposes to aid the reader's understanding ofthe present disclosure, and do not create limitations, particularly asto the position, orientation, or use of the disclosure. Connectionreferences (e.g., attached, coupled, connected, and joined) are to beconstrued broadly and may include intermediate members between acollection of elements and relative movement between elements unlessotherwise indicated. As such, connection references do not necessarilyinfer that two elements are directly connected and in fixed relation toeach other. It should be noted that delivery sheath and deliverycatheter may be used interchangeably for purposes of this description.The exemplary drawings are for purposes of illustration only and thedimensions, positions, order and relative sizes reflected in thedrawings attached hereto may vary.

U.S. Patent Application Pub. No. US 2016/0051801 is incorporated hereinby reference. U.S. Pat. No. 8,435,204 is incorporated herein byreference. U.S. Patent Application No. 62/568,412 (Attorney docketnumber 1421.1010100) is incorporated herein by reference. U.S. PatentApplication No. 62/598,846 (Attorney docket number 1421.1011100) isincorporated herein by reference.

The above specification, examples and data provide a completedescription of the structure and use of exemplary embodiments of thedisclosure as claimed below. Although various embodiments of thedisclosure as claimed have been described above with a certain degree ofparticularity, or with reference to one or more individual embodiments,those skilled in the art could make numerous alterations to thedisclosed embodiments without departing from the spirit or scope of thisdisclosure. Other embodiments are therefore contemplated. It is intendedthat all matter contained in the above description and shown in theaccompanying drawings shall be interpreted as illustrative only ofparticular embodiments and not limiting. Changes in detail or structuremay be made without departing from the basic elements of the disclosure.

What is claimed is:
 1. An inflammation management system, the systemcomprising: a controller; a cerebrospinal fluid management module incommunication with the controller; wherein the controller is configuredto: monitor measurements of one or more physiological parameters of apatient; compare a value related to the monitored measurements of theone or more physiological parameters to a threshold value; and controlthe cerebrospinal fluid management module based on the comparison of thevalue related to the monitored measurements of the one or morephysiological parameters to the threshold value.
 2. The system of claim1, wherein the controller is configured to automatically control thecerebrospinal fluid management module to perform a treatment oncerebrospinal fluid of the patient when the value related to themonitored measurements of the one or more physiological parametersreaches or goes beyond the threshold value.
 3. The system of claim 2,wherein the treatment on cerebrospinal fluid of the patient is apredetermined treatment based on one or both of: a type of physiologicalparameter associated with the monitored measurements; and the comparisonof the value related to the monitored measurements of the one or morephysiological parameters.
 4. The system of claim 1, wherein the valuerelated to the monitored measurements of the one or more physiologicalparameters is an indexed value related to measurements of two or morephysiological parameters of the patient.
 5. The system of claim 4,wherein the indexed value is a value of an index based on measurementsof the two or more physiological parameters of the patient.
 6. Thesystem of claim 1, wherein the one or more physiological parametersinclude one or more physiological parameters selected from a groupconsisting of intracranial pressure, cerebral pressure perfusion, meanarterial pressure, heart rate, brain oxygenation, cerebral blood flow,and a cytokine level.
 7. The system of claim 1, wherein thecerebrospinal fluid management module comprises one or both of: acooling treatment module; and a filtration treatment module.
 8. Thesystem of claim 1, wherein the cerebrospinal fluid management modulecomprises a circulation module having a pump configured to pumpcerebrospinal fluid from the patient to a treatment module.
 9. Thesystem of claim 1, further comprising: a user interface in communicationwith the controller; wherein the user interface is configured to:receive inputs that modify an operation of the controller; and display amedical image of the patient in a selectable pane and one or both of themeasurements of the one or more physiological parameters of a patientand the value related to the monitored measurements of the one or morephysiological parameters in a real-time updating pane position on theuser interface adjacent the selectable pane.
 10. A method of managinginflammation, the method comprising: monitoring measurements of one ormore physiological parameters of a patient over time; comparing a valuerelated to the monitored measurements of the one or more physiologicalparameters to a threshold value; and adjusting operation of acerebrospinal fluid management module based on the comparison of thevalue related to the monitored measurements of the one or morephysiological parameters to the threshold value.
 11. The method of claim10, further comprising: determining a difference between the valuerelated to the monitored measurements of the one or more physiologicalparameters and the threshold value; and wherein the adjusting operationof the cerebrospinal fluid management module is based on the determineddifference between the value related to the monitored measurements ofthe one or more physiological parameters and the threshold value. 12.The method of claim 10, wherein the adjusting operation of acerebrospinal fluid management module initiates a treatment startprotocol in response to the value related to the monitored measurementsof the one or more physiological parameters reaching or going beyond thethreshold value a first time.
 13. The method of claim 10, wherein theadjusting operation of a cerebrospinal fluid management module initiatesa treatment stop protocol in response to the value related to themonitored measurements of the one or more physiological parametersreaching or going beyond the threshold value.
 14. The method of claim10, wherein the adjusting operation of a cerebrospinal fluid managementmodule initiates a predetermined treatment protocol based on one or bothof: a type of physiological parameter associated with the monitoredmeasurements; and the comparison of the value related to the monitoredmeasurements of the one or more physiological parameters to thethreshold value.
 15. The method of claim 10, wherein the adjustingoperation of a cerebrospinal fluid management module causes thecerebrospinal fluid management module to initiate one or both of: acooling treatment protocol; and a filtration treatment protocol.
 16. Acomputer readable medium having stored thereon in a non-transitory statea program code for use by a computing device, the program code causingthe computing device to execute a method for managing inflammationcomprising: determining a value related to one or more measurements ofone or more physiological parameters; comparing the value related to theone or more measurements of the one or more physiological parameters toa threshold value; and outputting a control signal to adjust operationof a cerebrospinal fluid management module based on the comparison ofthe value related to the one or more measurements of the one or morephysiological parameters to the threshold value.
 17. The computerreadable medium of claim 16, the method further comprising: determininga difference between the value related to the one or more measurementsof the one or more physiological parameters and the threshold value;wherein the control signal adjusting operation of the cerebrospinalfluid management module is based on the determined difference betweenthe value related to the one or more measurements of the one or morephysiological parameters and the threshold value.
 18. The computerreadable medium of claim 17, wherein the outputted control signaladjusting operation of a cerebrospinal fluid management module isconfigured to initiate a treatment start protocol in response to thevalue related to the one or more measurements of the one or morephysiological parameters reaching or going beyond the threshold value afirst time.
 19. The computer readable medium of claim 17, wherein theoutputted control signal adjusting operation of a cerebrospinal fluidmanagement module is configured to initiate a treatment stop protocol inresponse to the value related to the one or more measurements of the oneor more physiological parameters reaching or going beyond the thresholdvalue.
 20. The computer readable medium of claim 17, wherein theoutputted control signal adjusting operation of a cerebrospinal fluidmanagement module is configured to initiate a predetermined treatmentprotocol based on one or both of: a type of physiological parameterassociated with the one or more measurements; and the comparison of thevalue related to the one or more measurements of the one or morephysiological parameters to the threshold value.